Advertisement

Chemical Modifications and Their Role in Long Non-coding RNAs

  • Sindy Zander
  • Roland Jacob
  • Tony GutschnerEmail author
Chapter

Abstract

The advent of next-generation sequencing technologies (NGS) in the last two decades combined with the elaborate implementation of algorithms as well as huge leaps in computing power shed light on the complex world of nucleic acids besides DNA. Tantalizingly, about 70–90% of the human genome is transcribed, but only ~2% is translated into proteins. Therefore, non-translated transcripts represent the overwhelming majority of the transcriptome, and they received the much-needed attention in the past decade. Several studies demonstrated the involvement of long noncoding RNAs (lncRNAs) in a vast number of cellular signaling pathways. Moreover, they play an active role in the regulation of gene expression utilizing varied ways of molecular mechanisms. Recently, the sophisticated application of NGS techniques paved the way for the transcriptome-wide characterization of different types of posttranscriptional chemical modifications of RNAs. These non-genomically encoded alterations expand the wide variety of the transcriptome even further. They influence important properties of transcripts, i.e., localization and stability, thereby modulating key cellular processes like translation, gene regulation, and metabolism. Despite great advances in the field and huge gains in knowledge about RNA modifications, most of the way to a comprehensive understanding needs still to be mastered.

In this chapter, the three most common RNA modifications, namely, N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ), will be the center of attention. At first we will give an overview of writers, readers, and erasers of those modifications, and then we will briefly summarize methods for their detection. Ultimately, we will introduce modifications on selected, cancer-related lncRNAs.

Keywords

Cancer lncRNA Noncoding RNA Epitranscriptome 5-Methylcytosine N6-methyladenosine Pseudouridine 

Abbreviations

4-SU

4-Thiouridine

Ψ

Pseudouridine

ALKBH5

Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5

ALL

Acute lymphoblastic leukemia

ALYREF

Aly/REF export factor

AML

Acute myeloid leukemia

ANLL

Acute nonlymphoblastic leukemia

ANRIL

Antisense non-coding RNA in the INK4 locus

APTR

Alu-mediated CDKN1A/p21 transcriptional regulator

ARE

AU-rich element

Aza-IP

5-Azacytidine-mediated RNA immunoprecipitation

CeU-seq

N3-CMC-enriched pseudouridine sequencing

CIMS

Cross-linking-induced mutation site

CITS

Cross-linking-induced truncation site

CMCT

N-Cyclohexyl-N′-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate

CML

Chronic myeloid leukemia

CoREST

Corepressor of RE1-silencing transcription factor

CRC

Colorectal cancer

DICER1-AS1

DICER1 antisense RNA 1

DKC1

Dyskerin pseudouridine synthase 1

DLEU2L

Deleted in lymphocytic leukemia 2-like

DNMT2

DNA methyltransferase-2

eIF3

Eukaryotic initiation factor 3

eIF4E

Eukaryotic initiation factor 4E

EMT

Epithelial-mesenchymal transition

FTO

Fat mass- and obesity-associated protein

GAS5

Growth arrest-specific 5

GBM

Glioblastoma

GSC

Glioblastoma stem-like cells

H3K27

Histone H3 lysine-27

H3K4

Histone H3 lysine-4

hnRNP U

Heterogeneous nuclear ribonucleoprotein U

HNRNPA2B1

Heterogeneous nuclear ribonucleoprotein A2/B1

HNRNPC

Heterogeneous nuclear ribonucleoprotein C

HOTAIR

HOX antisense intergenic RNA

HOXC/D

Homeobox C/D

HuR

Human antigen R

iCLIP

Individual-nucleotide-resolution cross-linking and immunoprecipitation

lncRNA

Long non-coding RNA

LRRC75C-AS1

LRRC75A antisense RNA1

LSD1

Lysine-specific demethylase 1A

m5C

5-Methylcytosine

m6A

N6-Methyladenosine

m6Am

N6,2′-O-Dimethyladenosine

MAGI2-AS3

MAGI2 antisense RNA 3

MALAT1

Metastasis-associated lung adenocarcinoma transcript 1

mascRNA

MALAT1-associated small cytoplasmic RNA

MAT2A

Methionine adenosyltransferase 2A

MDS

Myelodysplastic syndrome

MeRIP-Seq

M6A-specific methylated RNA immunoprecipitation sequencing

METTL

Methyltransferase-like protein

miRNA

MicroRNA

MPN

Myeloproliferative neoplasm

mRNA

Messenger RNA

MS

Mass spectrometry

mt

Mitochondrial

ncRNA

Non-coding RNA

NEAT1

Nuclear paraspeckle assembly transcript 1

NEAT2

Nuclear-enriched abundant transcript 2

NGS

Next-generation sequencing

NSCLC

Non-small cell lung cancer

NSUN

NOP2/Sun RNA methyltransferase family member

nt

Nucleotide

PA-m6A-seq

Photo-cross-linking-assisted m6A sequencing

PcG

Polycomb group

piRNA

PIWI-interacting RNA

PRC2

Polycomb-repressive complex 2

PTM

Posttranslational modification

PUS

Pseudouridine synthase

PUS7L

Pseudouridylate synthase 7-like

PUSL1

Pseudouridylate synthase-like 1

PVT1

Pvt1 oncogene

RAR

Retinoic acid receptor

RBP

RNA-binding protein

REST

RE1-silencing transcription factor

RMB15

RNA-binding motif protein 15

RMT

RNA methyltransferase

RN7SK

RNA 7SK small nuclear

RPPH1

Ribonuclease P RNA component H1

RPUSD

RNA pseudouridylate synthase domain containing

rRNA

Ribosomal RNA

RT-PCR

Reverse transcription-polymerase chain reaction

SAM

S-Adenosyl methionine

SCARLET

Site-specific cleavage and radioactive labeling followed by ligation-assisted extraction and thin-layer chromatography

siRNA

Small interfering RNA

SNHG

Small nucleolar RNA host gene

snoRNA

Small nucleolar RNA

snRNA

Small nuclear RNA

SPEN

Spen family transcriptional repressor

SRA

Steroid receptor RNA activator

SRAP

Steroid receptor RNA activator protein

ST7-AS1

ST7 antisense RNA 1

TERC

Telomerase RNA component

tRNA

Transfer RNA

TRUB

TruB pseudouridine synthase family member

TUG1

Taurine upregulated 1

UTR

Untranslated region

VIRMA

Vir-like m6A methyltransferase associated

WTAP

Wilms’ tumor 1-associating protein

XIC

X-inactivation center

XIST

X-inactive-specific transcript

YTHDC

YTH domain-containing protein

YTHDF

YT521-B homology domain family

ZFAS1

ZNFX1 antisense RNA 1

Notes

Acknowledgments

We apologize to all scientists whose important work could not be cited in this review due to space constraints. The authors wish to thank Monika Hämmerle for critical reading of the manuscript. Research in the Gutschner lab is supported by funds from the intramural Wilhelm-Roux Program of the Medical Faculty, Martin-Luther-University Halle-Wittenberg.

Author Contributions

Sindy Zander and Roland Jacob wrote the manuscript and prepared figures and tables. Tony Gutschner conceptualized and edited the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Abbasi-Moheb, L., Mertel, S., Gonsior, M., Nouri-Vahid, L., Kahrizi, K., Cirak, S., Wieczorek, D., Motazacker, M. M., Esmaeeli-Nieh, S., Cremer, K., Weissmann, R., Tzschach, A., Garshasbi, M., Abedini, S. S., Najmabadi, H., Ropers, H. H., Sigrist, S. J., & Kuss, A. W. (2012). Mutations in NSUN2 cause autosomal-recessive intellectual disability. American Journal of Human Genetics, 90, 847–855.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alarcon, C. R., Goodarzi, H., Lee, H., Liu, X., Tavazoie, S., & Tavazoie, S. F. (2015). HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell, 162, 1299–1308.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Amort, T., Souliere, M. F., Wille, A., Jia, X. Y., Fiegl, H., Worle, H., Micura, R., & Lusser, A. (2013). Long non-coding RNAs as targets for cytosine methylation. RNA Biology, 10, 1003–1008.PubMedCrossRefPubMedCentralGoogle Scholar
  4. Amort, T., Rieder, D., Wille, A., Khokhlova-Cubberley, D., Riml, C., Trixl, L., Jia, X. Y., Micura, R., & Lusser, A. (2017). Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biology, 18, 1.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Antonicka, H., Choquet, K., Lin, Z. Y., Gingras, A. C., Kleinman, C. L., & Shoubridge, E. A. (2017). A pseudouridine synthase module is essential for mitochondrial protein synthesis and cell viability. EMBO Reports, 18, 28–38.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Arguello, A. E., DeLiberto, A. N., & Kleiner, R. E. (2017). RNA chemical proteomics reveals the N(6)-Methyladenosine (m(6)A)-regulated protein-RNA Interactome. Journal of the American Chemical Society, 139, 17249–17252.PubMedCrossRefPubMedCentralGoogle Scholar
  7. Barbieri, I., Tzelepis, K., Pandolfini, L., Shi, J., Millan-Zambrano, G., Robson, S. C., Aspris, D., Migliori, V., Bannister, A. J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C. R., Vassiliou, G. S., & Kouzarides, T. (2017). Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature, 552, 126–131.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bartosovic, M., Molares, H. C., Gregorova, P., Hrossova, D., Kudla, G., & Vanacova, S. (2017). N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3′-end processing. Nucleic Acids Research, 45, 11356–11370.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Berger, S. L., Kouzarides, T., Shiekhattar, R., & Shilatifard, A. (2009). An operational definition of epigenetics. Genes & Development, 23, 781–783.CrossRefGoogle Scholar
  10. Bernard, D., Prasanth, K. V., Tripathi, V., Colasse, S., Nakamura, T., Xuan, Z., Zhang, M. Q., Sedel, F., Jourdren, L., Coulpier, F., Triller, A., Spector, D. L., & Bessis, A. (2010). A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. The EMBO Journal, 29, 3082–3093.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bokar, J. A., Shambaugh, M. E., Polayes, D., Matera, A. G., & Rottman, F. M. (1997). Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA, 3, 1233–1247.PubMedPubMedCentralGoogle Scholar
  12. Brockdorff, N., Ashworth, A., Kay, G. F., McCabe, V. M., Norris, D. P., Cooper, P. J., Swift, S., & Rastan, S. (1992). The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell, 71, 515–526.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Brown, C. J., Ballabio, A., Rupert, J. L., Lafreniere, R. G., Grompe, M., Tonlorenzi, R., & Willard, H. F. (1991). A gene from the region of the human X inactivation Centre is expressed exclusively from the inactive X chromosome. Nature, 349, 38–44.CrossRefGoogle Scholar
  14. Brown, J. A., Kinzig, C. G., DeGregorio, S. J., & Steitz, J. A. (2016). Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA. Proceedings of the National Academy of Sciences of the United States of America, 113, 14013–14018.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Brzezicha, B., Schmidt, M., Makalowska, I., Jarmolowski, A., Pienkowska, J., & Szweykowska-Kulinska, Z. (2006). Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Research, 34, 6034–6043.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bykhovskaya, Y., Casas, K., Mengesha, E., Inbal, A., & Fischel-Ghodsian, N. (2004). Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). American Journal of Human Genetics, 74, 1303–1308.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cantara, W. A., Crain, P. F., Rozenski, J., McCloskey, J. A., Harris, K. A., Zhang, X., Vendeix, F. A., Fabris, D., & Agris, P. F. (2011). The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Research, 39, D195–D201.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Carlile, T. M., Rojas-Duran, M. F., Zinshteyn, B., Shin, H., Bartoli, K. M., & Gilbert, W. V. (2014). Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature, 515, 143–146.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cech, T. R., & Steitz, J. A. (2014). The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 157, 77–94.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Charette, M., & Gray, M. W. (2000). Pseudouridine in RNA: What, where, how, and why. IUBMB Life, 49, 341–351.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chen, L. L., & Carmichael, G. G. (2010). Long noncoding RNAs in mammalian cells: What, where, and why? Wiley Interdisciplinary Reviews RNA, 1, 2–21.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Chen, K., Lu, Z., Wang, X., Fu, Y., Luo, G.-Z., Liu, N., Han, D., Dominissini, D., Dai, Q., Pan, T., & He, C. (2015). High-resolution N(6)-Methyladenosine (m(6)A) map using photo-crosslinking-assisted m(6)A sequencing(). Angewandte Chemie, 54, 1587–1590.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Chen, D. L., Chen, L. Z., Lu, Y. X., Zhang, D. S., Zeng, Z. L., Pan, Z. Z., Huang, P., Wang, F. H., Li, Y. H., Ju, H. Q., & Xu, R. H. (2017). Long noncoding RNA XIST expedites metastasis and modulates epithelial-mesenchymal transition in colorectal cancer. Cell Death & Disease, 8, e3011.CrossRefGoogle Scholar
  24. Chu, C., Zhang, Q. C., da Rocha, S. T., Flynn, R. A., Bharadwaj, M., Calabrese, J. M., Magnuson, T., Heard, E., & Chang, H. Y. (2015). Systematic discovery of Xist RNA binding proteins. Cell, 161, 404–416.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Cohn, W. E., & Volkin, E. (1951). Nucleoside-5[prime]-phosphates from ribonucleic acid. Nature, 167, 483–484.CrossRefGoogle Scholar
  26. Csepany, T., Lin, A., Baldick, C. J., Jr., & Beemon, K. (1990). Sequence specificity of mRNA N6-adenosine methyltransferase. The Journal of Biological Chemistry, 265, 20117–20122.PubMedPubMedCentralGoogle Scholar
  27. Cui, Q., Shi, H., Ye, P., Li, L., Qu, Q., Sun, G., Sun, G., Lu, Z., Huang, Y., Yang, C. G., Riggs, A. D., He, C., & Shi, Y. (2017). m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Reports, 18, 2622–2634.PubMedPubMedCentralCrossRefGoogle Scholar
  28. da Rocha, S. T., & Heard, E. (2017). Novel players in X inactivation: Insights into Xist-mediated gene silencing and chromosome conformation. Nature Structural & Molecular Biology, 24, 197–204.CrossRefGoogle Scholar
  29. Dai, D., Wang, H., Zhu, L., Jin, H., & Wang, X. (2018). N6-methyladenosine links RNA metabolism to cancer progression. Cell Death & Disease, 9, 124.CrossRefGoogle Scholar
  30. Davis, D. R. (1995). Stabilization of RNA stacking by pseudouridine. Nucleic Acids Research, 23, 5020–5026.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Desrosiers, R., Friderici, K., & Rottman, F. (1974). Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proceedings of the National Academy of Sciences of the United States of America, 71, 3971–3975.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Dhamija, S., & Diederichs, S. (2016). From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis. International Journal of Cancer, 139, 269–280.PubMedCrossRefPubMedCentralGoogle Scholar
  33. Diederichs, S., Bartsch, L., Berkmann, J. C., Frose, K., Heitmann, J., Hoppe, C., Iggena, D., Jazmati, D., Karschnia, P., Linsenmeier, M., Maulhardt, T., Mohrmann, L., Morstein, J., Paffenholz, S. V., Ropenack, P., Ruckert, T., Sandig, L., Schell, M., Steinmann, A., Voss, G., Wasmuth, J., Weinberger, M. E., & Wullenkord, R. (2016). The dark matter of the cancer genome: aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations. EMBO Molecular Medicine, 8, 442–457.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Dinger, M. E., Pang, K. C., Mercer, T. R., & Mattick, J. S. (2008). Differentiating protein-coding and noncoding RNA: Challenges and ambiguities. PLoS Computational Biology, 4, e1000176.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S., Salmon-Divon, M., Ungar, L., Osenberg, S., Cesarkas, K., Jacob-Hirsch, J., Amariglio, N., Kupiec, M., Sorek, R., & Rechavi, G. (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485, 201–206.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dominissini, D., Moshitch-Moshkovitz, S., Amariglio, N., & Rechavi, G. (2015). Transcriptome-wide mapping of N(6)-Methyladenosine by m(6)A-Seq. Methods in Enzymology, 560, 131–147.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Durairaj, A., & Limbach, P. A. (2008). Mass spectrometry of the fifth nucleoside: A review of the identification of pseudouridine in nucleic acids. Analytica Chimica Acta, 623, 117–125.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Edelheit, S., Schwartz, S., Mumbach, M. R., Wurtzel, O., & Sorek, R. (2013). Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m5C within archaeal mRNAs. PLoS Genetics, 9, e1003602.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Edupuganti, R. R., Geiger, S., Lindeboom, R. G. H., Shi, H., Hsu, P. J., Lu, Z., Wang, S. Y., Baltissen, M. P. A., Jansen, P., Rossa, M., Muller, M., Stunnenberg, H. G., He, C., Carell, T., & Vermeulen, M. (2017). N(6)-methyladenosine (m(6)A) recruits and repels proteins to regulate mRNA homeostasis. Nature Structural & Molecular Biology, 24, 870–878.CrossRefGoogle Scholar
  40. Eissmann, M., Gutschner, T., Hammerle, M., Gunther, S., Caudron-Herger, M., Gross, M., Schirmacher, P., Rippe, K., Braun, T., Zornig, M., & Diederichs, S. (2012). Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biology, 9, 1076–1087.PubMedPubMedCentralCrossRefGoogle Scholar
  41. ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57–74.CrossRefGoogle Scholar
  42. Forbes, S. A., Beare, D., Boutselakis, H., Bamford, S., Bindal, N., Tate, J., Cole, C. G., Ward, S., Dawson, E., Ponting, L., Stefancsik, R., Harsha, B., Kok, C. Y., Jia, M., Jubb, H., Sondka, Z., Thompson, S., De, T., & Campbell, P. J. (2017). COSMIC: Somatic cancer genetics at high-resolution. Nucleic Acids Research, 45, D777–D783.PubMedCrossRefPubMedCentralGoogle Scholar
  43. Forrest, M. E., Saiakhova, A., Beard, L., Buchner, D. A., Scacheri, P. C., LaFramboise, T., Markowitz, S., & Khalil, A. M. (2018). Colon cancer-upregulated long non-coding RNA lincDUSP regulates cell cycle genes and potentiates resistance to apoptosis. Scientific Reports, 8, 7324.PubMedPubMedCentralCrossRefGoogle Scholar
  44. Frye, M., & Watt, F. M. (2006). The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Current Biology, 16, 971–981.PubMedCrossRefPubMedCentralGoogle Scholar
  45. Frye, M., Jaffrey, S. R., Pan, T., Rechavi, G., & Suzuki, T. (2016). RNA modifications: What have we learned and where are we headed? Nature Reviews Genetics, 17, 365–372.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Fustin, J. M., Doi, M., Yamaguchi, Y., Hida, H., Nishimura, S., Yoshida, M., Isagawa, T., Morioka, M. S., Kakeya, H., Manabe, I., & Okamura, H. (2013). RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell, 155, 793–806.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Ge, J., & Yu, Y. T. (2013). RNA pseudouridylation: New insights into an old modification. Trends in Biochemical Sciences, 38, 210–218.PubMedPubMedCentralCrossRefGoogle Scholar
  48. Glasner, H., Riml, C., Micura, R., & Breuker, K. (2017). Label-free, direct localization and relative quantitation of the RNA nucleobase methylations m6A, m5C, m3U, and m5U by top-down mass spectrometry. Nucleic Acids Research, 45, 8014–8025.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Goll, M. G., Kirpekar, F., Maggert, K. A., Yoder, J. A., Hsieh, C. L., Zhang, X., Golic, K. G., Jacobsen, S. E., & Bestor, T. H. (2006). Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science, 311, 395–398.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Gupta, R. A., Shah, N., Wang, K. C., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M. C., Hung, T., Argani, P., Rinn, J. L., Wang, Y., Brzoska, P., Kong, B., Li, R., West, R. B., van de Vijver, M. J., Sukumar, S., & Chang, H. Y. (2010). Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature, 464, 1071–1076.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gutschner, T., & Diederichs, S. (2012). The hallmarks of cancer: A long non-coding RNA point of view. RNA Biology, 9, 703–719.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gutschner, T., Baas, M., & Diederichs, S. (2011). Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases. Genome Research, 21, 1944–1954.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Gutschner, T., Hammerle, M., & Diederichs, S. (2013a). MALAT1—a paradigm for long noncoding RNA function in cancer. Journal of Molecular Medicine, 91, 791–801.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Gutschner, T., Hammerle, M., Eissmann, M., Hsu, J., Kim, Y., Hung, G., Revenko, A., Arun, G., Stentrup, M., Gross, M., Zornig, M., MacLeod, A. R., Spector, D. L., & Diederichs, S. (2013b). The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Research, 73, 1180–1189.CrossRefGoogle Scholar
  55. Guttman, M., Amit, I., Garber, M., French, C., Lin, M. F., Feldser, D., Huarte, M., Zuk, O., Carey, B. W., Cassady, J. P., Cabili, M. N., Jaenisch, R., Mikkelsen, T. S., Jacks, T., Hacohen, N., Bernstein, B. E., Kellis, M., Regev, A., Rinn, J. L., & Lander, E. S. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 458, 223–227.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Haag, S., Warda, A. S., Kretschmer, J., Gunnigmann, M. A., Hobartner, C., & Bohnsack, M. T. (2015). NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA, 21, 1532–1543.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Haag, S., Sloan, K. E., Ranjan, N., Warda, A. S., Kretschmer, J., Blessing, C., Hubner, B., Seikowski, J., Dennerlein, S., Rehling, P., Rodnina, M. V., Hobartner, C., & Bohnsack, M. T. (2016). NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation. The EMBO Journal, 35, 2104–2119.PubMedPubMedCentralCrossRefGoogle Scholar
  58. Haemmerle, M., & Gutschner, T. (2015). Long non-coding RNAs in cancer and development: Where do we go from here? International Journal of Molecular Sciences, 16, 1395–1405.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Harris, T., Marquez, B., Suarez, S., & Schimenti, J. (2007). Sperm motility defects and infertility in male mice with a mutation in Nsun7, a member of the Sun domain-containing family of putative RNA methyltransferases. Biology of Reproduction, 77, 376–382.PubMedCrossRefPubMedCentralGoogle Scholar
  60. Hasegawa, Y., Brockdorff, N., Kawano, S., Tsutui, K., Tsutui, K., & Nakagawa, S. (2010). The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Developmental Cell, 19, 469–476.CrossRefGoogle Scholar
  61. He, Y., Hu, H., Wang, Y., Yuan, H., Lu, Z., Wu, P., Liu, D., Tian, L., Yin, J., Jiang, K., & Miao, Y. (2018). ALKBH5 inhibits pancreatic cancer motility by decreasing long non-coding RNA KCNK15-AS1 methylation. Cellular Physiology and Biochemistry, 48, 838–846.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Heinemann, A., Zhao, F., Pechlivanis, S., Eberle, J., Steinle, A., Diederichs, S., Schadendorf, D., & Paschen, A. (2012). Tumor suppressive microRNAs miR-34a/c control cancer cell expression of ULBP2, a stress-induced ligand of the natural killer cell receptor NKG2D. Cancer Research, 72, 460–471.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Heiss, N. S., Knight, S. W., Vulliamy, T. J., Klauck, S. M., Wiemann, S., Mason, P. J., Poustka, A., & Dokal, I. (1998). X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nature Genetics, 19, 32–38.PubMedCrossRefPubMedCentralGoogle Scholar
  64. Helm, M., & Alfonzo, J. D. (2014). Posttranscriptional RNA modifications: Playing metabolic games in a cell’s chemical Legoland. Chemistry & Biology, 21, 174–185.CrossRefGoogle Scholar
  65. Helm, M., & Motorin, Y. (2017). Detecting RNA modifications in the epitranscriptome: Predict and validate. Nature Reviews Genetics., 18, 275–291.PubMedCrossRefPubMedCentralGoogle Scholar
  66. Hotchkiss, R. D. (1948). The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. The Journal of Biological Chemistry, 175, 315–332.PubMedPubMedCentralGoogle Scholar
  67. Hsu, P. J., & He, C. (2018). Identifying the m(6)A Methylome by affinity purification and sequencing. Methods in Molecular Biology (Clifton, NJ), 1649, 49–57.CrossRefGoogle Scholar
  68. Huang, H., Weng, H., Sun, W., Qin, X., Shi, H., Wu, H., Zhao, B. S., Mesquita, A., Liu, C., Yuan, C. L., Hu, Y. C., Huttelmaier, S., Skibbe, J. R., Su, R., Deng, X., Dong, L., Sun, M., Li, C., Nachtergaele, S., Wang, Y., Hu, C., Ferchen, K., Greis, K. D., Jiang, X., Wei, M., Qu, L., Guan, J. L., He, C., Yang, J., & Chen, J. (2018). Recognition of RNA N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nature Cell Biology., 20, 285–295.PubMedPubMedCentralCrossRefGoogle Scholar
  69. Huarte, M., Guttman, M., Feldser, D., Garber, M., Koziol, M. J., Kenzelmann-Broz, D., Khalil, A. M., Zuk, O., Amit, I., Rabani, M., Attardi, L. D., Regev, A., Lander, E. S., Jacks, T., & Rinn, J. L. (2010). A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell, 142, 409–419.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Hube, F., Guo, J., Chooniedass-Kothari, S., Cooper, C., Hamedani, M. K., Dibrov, A. A., Blanchard, A. A., Wang, X., Deng, G., Myal, Y., & Leygue, E. (2006). Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. DNA and Cell Biology, 25, 418–428.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Hussain, S., Sajini, A. A., Blanco, S., Dietmann, S., Lombard, P., Sugimoto, Y., Paramor, M., Gleeson, J. G., Odom, D. T., Ule, J., & Frye, M. (2013). NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Reports, 4, 255–261.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Hutchinson, J. N., Ensminger, A. W., Clemson, C. M., Lynch, C. R., Lawrence, J. B., & Chess, A. (2007). A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics, 8, 39.PubMedPubMedCentralCrossRefGoogle Scholar
  73. Iyer, M. K., Niknafs, Y. S., Malik, R., Singhal, U., Sahu, A., Hosono, Y., Barrette, T. R., Prensner, J. R., Evans, J. R., Zhao, S., Poliakov, A., Cao, X., Dhanasekaran, S. M., Wu, Y. M., Robinson, D. R., Beer, D. G., Feng, F. Y., Iyer, H. K., & Chinnaiyan, A. M. (2015). The landscape of long noncoding RNAs in the human transcriptome. Nature Genetics, 47, 199–208.PubMedPubMedCentralCrossRefGoogle Scholar
  74. Jeltsch, A., Ehrenhofer-Murray, A., Jurkowski, T. P., Lyko, F., Reuter, G., Ankri, S., Nellen, W., Schaefer, M., & Helm, M. (2016). Mechanism and biological role of Dnmt2 in nucleic acid methylation. RNA Biology, 14, 1–16.Google Scholar
  75. Ji, P., Diederichs, S., Wang, W., Boing, S., Metzger, R., Schneider, P. M., Tidow, N., Brandt, B., Buerger, H., Bulk, E., Thomas, M., Berdel, W. E., Serve, H., & Muller-Tidow, C. (2003). MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22, 8031–8041.PubMedCrossRefPubMedCentralGoogle Scholar
  76. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y. G., & He, C. (2011). N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nature Chemical Biology, 7, 885–887.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Jonkhout, N., Tran, J., Smith, M. A., Schonrock, N., Mattick, J. S., & Novoa, E. M. (2017). The RNA modification landscape in human disease. RNA, 23(12), 1754–1769.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Kahlert, C., Klupp, F., Brand, K., Lasitschka, F., Diederichs, S., Kirchberg, J., Rahbari, N., Dutta, S., Bork, U., Fritzmann, J., Reissfelder, C., Koch, M., & Weitz, J. (2011). Invasion front-specific expression and prognostic significance of microRNA in colorectal liver metastases. Cancer Science, 102, 1799–1807.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Kaiser, S., Jurkowski, T. P., Kellner, S., Schneider, D., Jeltsch, A., & Helm, M. (2016). The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA. RNA Biology, 14, 1–11.Google Scholar
  80. Karijolich, J., & Yu, Y. T. (2011). Converting nonsense codons into sense codons by targeted pseudouridylation. Nature, 474, 395–398.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Khalil, A. M., Guttman, M., Huarte, M., Garber, M., Raj, A., Rivea Morales, D., Thomas, K., Presser, A., Bernstein, B. E., van Oudenaarden, A., Regev, A., Lander, E. S., & Rinn, J. L. (2009). Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proceedings of the National Academy of Sciences of the United States of America, 106, 11667–11672.PubMedPubMedCentralCrossRefGoogle Scholar
  82. Khan, M. A., Rafiq, M. A., Noor, A., Hussain, S., Flores, J. V., Rupp, V., Vincent, A. K., Malli, R., Ali, G., Khan, F. S., Ishak, G. E., Doherty, D., Weksberg, R., Ayub, M., Windpassinger, C., Ibrahim, S., Frye, M., Ansar, M., & Vincent, J. B. (2012). Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. American Journal of Human Genetics, 90, 856–863.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Khoddami, V., & Cairns, B. R. (2013). Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nature Biotechnology, 31, 458–464.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Khoddami, V., & Cairns, B. R. (2014). Transcriptome-wide target profiling of RNA cytosine methyltransferases using the mechanism-based enrichment procedure Aza-IP. Nature Protocols, 9, 337–361.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Kierzek, E., & Kierzek, R. (2003). The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines. Nucleic Acids Research, 31, 4472–4480.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Knowling, S., & Morris, K. V. (2011). Non-coding RNA and antisense RNA. Nature’s trash or treasure? Biochimie, 93, 1922–1927.PubMedPubMedCentralCrossRefGoogle Scholar
  87. Kogo, R., Shimamura, T., Mimori, K., Kawahara, K., Imoto, S., Sudo, T., Tanaka, F., Shibata, K., Suzuki, A., Komune, S., Miyano, S., & Mori, M. (2011). Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Research, 71, 6320–6326.PubMedPubMedCentralCrossRefGoogle Scholar
  88. Kowalczyk, M. S., Higgs, D. R., & Gingeras, T. R. (2012). Molecular biology: RNA discrimination. Nature, 482, 310–311.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Kruger, K., Grabowski, P. J., Zaug, A. J., Sands, J., Gottschling, D. E., & Cech, T. R. (1982). Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell, 31, 147–157.CrossRefGoogle Scholar
  90. Lanz, R. B., McKenna, N. J., Onate, S. A., Albrecht, U., Wong, J., Tsai, S. Y., Tsai, M. J., & O’Malley, B. W. (1999). A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell, 97, 17–27.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Lanz, R. B., Razani, B., Goldberg, A. D., & O’Malley, B. W. (2002). Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proceedings of the National Academy of Sciences of the United States of America, 99, 16081–16086.PubMedPubMedCentralCrossRefGoogle Scholar
  92. Lanz, R. B., Chua, S. S., Barron, N., Soder, B. M., DeMayo, F., & O’Malley, B. W. (2003). Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Molecular and Cellular Biology, 23, 7163–7176.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Lassmann, S., Weis, R., Makowiec, F., Roth, J., Danciu, M., Hopt, U., & Werner, M. (2007). Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas. Journal of Molecular Medicine, 85, 293–304.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Leygue, E. (2007). Steroid receptor RNA activator (SRA1): Unusual bifaceted gene products with suspected relevance to breast cancer. Nuclear Receptor Signaling, 5, e006.PubMedPubMedCentralCrossRefGoogle Scholar
  95. Li, X., Zhu, P., Ma, S., Song, J., Bai, J., Sun, F., & Yi, C. (2015). Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nature Chemical Biology, 11, 592–597.PubMedCrossRefPubMedCentralGoogle Scholar
  96. Li, X., Ma, S., & Yi, C. (2016). Pseudouridine: The fifth RNA nucleotide with renewed interests. Current Opinion in Chemical Biology., 33, 108–116.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Li, Z., Weng, H., Su, R., Weng, X., Zuo, Z., Li, C., Huang, H., Nachtergaele, S., Dong, L., Hu, C., Qin, X., Tang, L., Wang, Y., Hong, G. M., Huang, H., Wang, X., Chen, P., Gurbuxani, S., Arnovitz, S., Li, Y., Li, S., Strong, J., Neilly, M. B., Larson, R. A., Jiang, X., Zhang, P., Jin, J., He, C., & Chen, J. (2017a). FTO plays an oncogenic role in acute myeloid leukemia as a N6-Methyladenosine RNA demethylase. Cancer Cell, 31, 127–141.CrossRefGoogle Scholar
  98. Li, N., Wang, Y., Liu, X., Luo, P., Jing, W., Zhu, M., & Tu, J. (2017b). Identification of circulating long noncoding RNA HOTAIR as a novel biomarker for diagnosis and monitoring of non-small cell lung Cancer. Technology in Cancer Research & Treatment, 16(6), 1060–1066.CrossRefGoogle Scholar
  99. Li, H., Yuan, X., Yan, D., Li, D., Guan, F., Dong, Y., Wang, H., Liu, X., & Yang, B. (2017c). Long non-coding RNA MALAT1 decreases the sensitivity of resistant glioblastoma cell lines to Temozolomide. Cellular Physiology and Biochemistry, 42, 1192–1201.PubMedCrossRefPubMedCentralGoogle Scholar
  100. Linder, B., Grozhik, A. V., Olarerin-George, A. O., Meydan, C., Mason, C. E., & Jaffrey, S. R. (2015). Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nature Methods, 12, 767–772.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Lipovich, L., Johnson, R., & Lin, C. Y. (2010). MacroRNA underdogs in a microRNA world: Evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochimica et Biophysica Acta, 1799, 597–615.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Liu, M., Roth, A., Yu, M., Morris, R., Bersani, F., Rivera, M. N., Lu, J., Shioda, T., Vasudevan, S., Ramaswamy, S., Maheswaran, S., Diederichs, S., & Haber, D. A. (2013a). The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes & Development, 27, 2543–2548.CrossRefGoogle Scholar
  103. Liu, N., Parisien, M., Dai, Q., Zheng, G., He, C., & Pan, T. (2013b). Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA, 19, 1848–1856.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X., Dai, Q., Chen, W., & He, C. (2014). A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nature Chemical Biology, 10, 93–95.PubMedCrossRefPubMedCentralGoogle Scholar
  105. Liu, N., Dai, Q., Zheng, G., He, C., Parisien, M., & Pan, T. (2015). N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature, 518, 560–564.PubMedPubMedCentralCrossRefGoogle Scholar
  106. Liu, C., Wu, H. T., Zhu, N., Shi, Y. N., Liu, Z., Ao, B. X., Liao, D. F., Zheng, X. L., & Qin, L. (2016). Steroid receptor RNA activator: Biologic function and role in disease. Clinica Chimica Acta, 459, 137–146.CrossRefGoogle Scholar
  107. Liu, D., Zhu, Y., Pang, J., Weng, X., Feng, X., & Guo, Y. (2017a). Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195. Journal of Cellular Biochemistry, 119(2), 1368–1380.PubMedCrossRefPubMedCentralGoogle Scholar
  108. Liu, N., Zhou, K. I., Parisien, M., Dai, Q., Diatchenko, L., & Pan, T. (2017b). N6-methyladenosine alters RNA structure to regulate binding of a low-complexity protein. Nucleic Acids Research, 45, 6051–6063.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Lovejoy, A. F., Riordan, D. P., & Brown, P. O. (2014). Transcriptome-wide mapping of pseudouridines: Pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLoS One, 9, e110799.PubMedPubMedCentralCrossRefGoogle Scholar
  110. Machnicka, M. A., Milanowska, K., Osman Oglou, O., Purta, E., Kurkowska, M., Olchowik, A., Januszewski, W., Kalinowski, S., Dunin-Horkawicz, S., Rother, K. M., Helm, M., Bujnicki, J. M., & Grosjean, H. (2013). MODOMICS: A database of RNA modification pathways--2013 update. Nucleic Acids Research, 41, D262–D267.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Martinez, F. J., Lee, J. H., Lee, J. E., Blanco, S., Nickerson, E., Gabriel, S., Frye, M., Al-Gazali, L., & Gleeson, J. G. (2012). Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. Journal of Medical Genetics, 49, 380–385.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Mauer, J., Luo, X., Blanjoie, A., Jiao, X., Grozhik, A. V., Patil, D. P., Linder, B., Pickering, B. F., Vasseur, J. J., Chen, Q., Gross, S. S., Elemento, O., Debart, F., Kiledjian, M., & Jaffrey, S. R. (2017). Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature, 541, 371–375.CrossRefGoogle Scholar
  113. McHugh, C. A., Chen, C. K., Chow, A., Surka, C. F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., Sweredoski, M. J., Shishkin, A. A., Su, J., Lander, E. S., Hess, S., Plath, K., & Guttman, M. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature, 521, 232–236.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Mei, Y. P., Liao, J. P., Shen, J., Yu, L., Liu, B. L., Liu, L., Li, R. Y., Ji, L., Dorsey, S. G., Jiang, Z. R., Katz, R. L., Wang, J. Y., & Jiang, F. (2012). Small nucleolar RNA 42 acts as an oncogene in lung tumorigenesis. Oncogene, 31, 2794–2804.PubMedPubMedCentralCrossRefGoogle Scholar
  115. Merry, C. R., Forrest, M. E., Sabers, J. N., Beard, L., Gao, X. H., Hatzoglou, M., Jackson, M. W., Wang, Z., Markowitz, S. D., & Khalil, A. M. (2015). DNMT1-associated long non-coding RNAs regulate global gene expression and DNA methylation in colon cancer. Human Molecular Genetics, 24, 6240–6253.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Metodiev, M. D., Spahr, H., Loguercio Polosa, P., Meharg, C., Becker, C., Altmueller, J., Habermann, B., Larsson, N. G., & Ruzzenente, B. (2014). NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genetics., 10, e1004110.PubMedPubMedCentralCrossRefGoogle Scholar
  117. Meyer, K. D., & Jaffrey, S. R. (2017). Rethinking m6A readers, writers, and erasers. Annual Review of Cell and Developmental Biology, 33, 319–342.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Meyer, K. D., Saletore, Y., Zumbo, P., Elemento, O., Mason, C. E., & Jaffrey, S. R. (2012). Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell, 149, 1635–1646.PubMedPubMedCentralCrossRefGoogle Scholar
  119. Meyer, K. D., Patil, D. P., Zhou, J., Zinoviev, A., Skabkin, M. A., Elemento, O., Pestova, T. V., Qian, S. B., & Jaffrey, S. R. (2015). 5′ UTR m(6)A promotes cap-independent translation. Cell, 163, 999–1010.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Minajigi, A., Froberg, J., Wei, C., Sunwoo, H., Kesner, B., Colognori, D., Lessing, D., Payer, B., Boukhali, M., Haas, W., & Lee, J. T. (2015). Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science, 349, aab2276.CrossRefGoogle Scholar
  121. Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T. B., & Brockdorff, N. (2015). A pooled shRNA screen identifies Rbm15, Spen, and Wtap as factors required for Xist RNA-mediated silencing. Cell Reports, 12, 562–572.PubMedPubMedCentralCrossRefGoogle Scholar
  122. Molinie, B., Wang, J., Lim, K. S., Hillebrand, R., Lu, Z. X., Van Wittenberghe, N., Howard, B. D., Daneshvar, K., Mullen, A. C., Dedon, P., Xing, Y., & Giallourakis, C. C. (2016). m(6)A-LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome. Nature Methods, 13, 692–698.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Nakagawa, S., Ip, J. Y., Shioi, G., Tripathi, V., Zong, X., Hirose, T., & Prasanth, K. V. (2012). Malat1 is not an essential component of nuclear speckles in mice. RNA, 18, 1487–1499.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Okamoto, M., Hirata, S., Sato, S., Koga, S., Fujii, M., Qi, G., Ogawa, I., Takata, T., Shimamoto, F., & Tatsuka, M. (2012). Frequent increased gene copy number and high protein expression of tRNA (cytosine-5-)-methyltransferase (NSUN2) in human cancers. DNA and Cell Biology, 31, 660–671.PubMedCrossRefPubMedCentralGoogle Scholar
  125. Pa, M., Naizaer, G., Seyiti, A., & Kuerbang, G. (2017). Long noncoding RNA MALAT1 functions as a sponge of MiR-200c in ovarian cancer. Oncology Research.  https://doi.org/10.3727/096504017X15049198963076.
  126. Pang, E. J., Yang, R., Fu, X. B., & Liu, Y. F. (2015). Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biology, 36, 2403–2407.PubMedCrossRefPubMedCentralGoogle Scholar
  127. Patil, D. P., Chen, C. K., Pickering, B. F., Chow, A., Jackson, C., Guttman, M., & Jaffrey, S. R. (2016). m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature, 537, 369–373.PubMedPubMedCentralCrossRefGoogle Scholar
  128. Patil, D. P., Pickering, B. F., & Jaffrey, S. R. (2018). Reading m(6)A in the transcriptome: m(6)A-binding proteins. Trends in Cell Biology, 28, 113–127.PubMedCrossRefPubMedCentralGoogle Scholar
  129. Patton, J. R., Bykhovskaya, Y., Mengesha, E., Bertolotto, C., & Fischel-Ghodsian, N. (2005). Mitochondrial myopathy and sideroblastic anemia (MLASA): Missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. The Journal of Biological Chemistry, 280, 19823–19828.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Pendleton, K. E., Chen, B., Liu, K., Hunter, O. V., Xie, Y., Tu, B. P., & Conrad, N. K. (2017). The U6 snRNA m6A methyltransferase METTL16 regulates SAM Synthetase intron retention. Cell, 169, 824–835.e14.PubMedPubMedCentralCrossRefGoogle Scholar
  131. Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S., & Brockdorff, N. (1996). Requirement for Xist in X chromosome inactivation. Nature, 379, 131–137.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Perry, R. P., & Kelley, D. E. (1974). Existence of methylated messenger RNA in mouse L cells. Cell, 1, 37–42.CrossRefGoogle Scholar
  133. Pfaff, C., Ehrnsberger, H. F., Flores-Tornero, M., Sorensen, B. B., Schubert, T., Langst, G., Griesenbeck, J., Sprunck, S., Grasser, M., & Grasser, K. D. (2018). ALY RNA-binding proteins are required for Nucleocytosolic mRNA transport and modulate plant growth and development. Plant Physiology, 177, 226–240.PubMedPubMedCentralGoogle Scholar
  134. Pichler, M., Stiegelbauer, V., Vychytilova-Faltejskova, P., Ivan, C., Ling, H., Winter, E., Zhang, X., Goblirsch, M., Wulf-Goldenberg, A., Ohtsuka, M., Haybaeck, J., Svoboda, M., Okugawa, Y., Gerger, A., Hoefler, G., Goel, A., Slaby, O., & Calin, G. A. (2017). Genome-wide miRNA analysis identifies miR-188-3p as a novel prognostic marker and molecular factor involved in colorectal carcinogenesis. Clinical Cancer Research, 23, 1323–1333.PubMedCrossRefPubMedCentralGoogle Scholar
  135. Ping, X. L., Sun, B. F., Wang, L., Xiao, W., Yang, X., Wang, W. J., Adhikari, S., Shi, Y., Lv, Y., Chen, Y. S., Zhao, X., Li, A., Yang, Y., Dahal, U., Lou, X. M., Liu, X., Huang, J., Yuan, W. P., Zhu, X. F., Cheng, T., Zhao, Y. L., Wang, X., Rendtlew Danielsen, J. M., Liu, F., & Yang, Y. G. (2014). Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Research, 24, 177–189.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Ponting, C. P., Oliver, P. L., & Reik, W. (2009). Evolution and functions of long noncoding RNAs. Cell, 136, 629–641.PubMedCrossRefPubMedCentralGoogle Scholar
  137. Prabakaran, S., Lippens, G., Steen, H., & Gunawardena, J. (2012). Post-translational modification: Nature’s escape from genetic imprisonment and the basis for dynamic information encoding. Wiley Interdisciplinary Reviews Systems Biology and Medicine, 4, 565–583.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Quek, X. C., Thomson, D. W., Maag, J. L., Bartonicek, N., Signal, B., Clark, M. B., Gloss, B. S., & Dinger, M. E. (2015). lncRNAdb v2.0: Expanding the reference database for functional long noncoding RNAs. Nucleic Acids Research, 43, D168–D173.PubMedCrossRefPubMedCentralGoogle Scholar
  139. Richtig, G., Ehall, B., Richtig, E., Aigelsreiter, A., Gutschner, T., & Pichler, M. (2017). Function and clinical implications of long non-coding RNAs in melanoma. International Journal of Molecular Sciences, 18, 715.PubMedPubMedCentralCrossRefGoogle Scholar
  140. Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P. J., Segal, E., & Chang, H. Y. (2007). Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell, 129, 1311–1323.PubMedPubMedCentralCrossRefGoogle Scholar
  141. Roost, C., Lynch, S. R., Batista, P. J., Qu, K., Chang, H. Y., & Kool, E. T. (2015). Structure and thermodynamics of N6-methyladenosine in RNA: A spring-loaded base modification. Journal of the American Chemical Society, 137, 2107–2115.PubMedPubMedCentralCrossRefGoogle Scholar
  142. Rose, R. E., Quinn, R., Sayre, J. L., & Fabris, D. (2015). Profiling ribonucleotide modifications at full-transcriptome level: A step toward MS-based epitranscriptomics. RNA, 21, 1361–1374.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Roundtree, I. A., Luo, G. Z., Zhang, Z., Wang, X., Zhou, T., Cui, Y., Sha, J., Huang, X., Guerrero, L., Xie, P., He, E., Shen, B., & He, C. (2017). YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. eLife, 6, e31311.PubMedPubMedCentralCrossRefGoogle Scholar
  144. Safra, M., Nir, R., Farouq, D., Vainberg Slutskin, I., & Schwartz, S. (2017a). TRUB1 is the predominant pseudouridine synthase acting on mammalian mRNA via a predictable and conserved code. Genome Research, 27, 393–406.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Safra, M., Sas-Chen, A., Nir, R., Winkler, R., Nachshon, A., Bar-Yaacov, D., Erlacher, M., Rossmanith, W., Stern-Ginossar, N., & Schwartz, S. (2017b). The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature, 551, 251–255.PubMedCrossRefPubMedCentralGoogle Scholar
  146. Schosserer, M., Minois, N., Angerer, T. B., Amring, M., Dellago, H., Harreither, E., Calle-Perez, A., Pircher, A., Gerstl, M. P., Pfeifenberger, S., Brandl, C., Sonntagbauer, M., Kriegner, A., Linder, A., Weinhausel, A., Mohr, T., Steiger, M., Mattanovich, D., Rinnerthaler, M., Karl, T., Sharma, S., Entian, K. D., Kos, M., Breitenbach, M., Wilson, I. B., Polacek, N., Grillari-Voglauer, R., Breitenbach-Koller, L., & Grillari, J. (2015). Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nature Communications, 6, 6158.PubMedPubMedCentralCrossRefGoogle Scholar
  147. Schwartz, S., Bernstein, D. A., Mumbach, M. R., Jovanovic, M., Herbst, R. H., Leon-Ricardo, B. X., Engreitz, J. M., Guttman, M., Satija, R., Lander, E. S., Fink, G., & Regev, A. (2014a). Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell, 159, 148–162.PubMedPubMedCentralCrossRefGoogle Scholar
  148. Schwartz, S., Mumbach, M. R., Jovanovic, M., Wang, T., Maciag, K., Bushkin, G. G., Mertins, P., Ter-Ovanesyan, D., Habib, N., Cacchiarelli, D., Sanjana, N. E., Freinkman, E., Pacold, M. E., Satija, R., Mikkelsen, T. S., Hacohen, N., Zhang, F., Carr, S. A., Lander, E. S., & Regev, A. (2014b). Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Reports, 8, 284–296.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Sharma, S., Yang, J., Watzinger, P., Kotter, P., & Entian, K. D. (2013). Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Research, 41, 9062–9076.PubMedPubMedCentralCrossRefGoogle Scholar
  150. Shen, P., Pichler, M., Chen, M., Calin, G. A., & Ling, H. (2017). To Wnt or lose: The missing non-coding Linc in colorectal Cancer. International Journal of Molecular Sciences, 18, 2003.CrossRefGoogle Scholar
  151. Sledz, P., & Jinek, M. (2016). Structural insights into the molecular mechanism of the m(6)A writer complex. eLife, 5, e18434.PubMedPubMedCentralCrossRefGoogle Scholar
  152. Spenkuch, F., Motorin, Y., & Helm, M. (2014). Pseudouridine: Still mysterious, but never a fake (uridine)! RNA Biology, 11, 1540–1554.PubMedCrossRefPubMedCentralGoogle Scholar
  153. Squires, J. E., Patel, H. R., Nousch, M., Sibbritt, T., Humphreys, D. T., Parker, B. J., Suter, C. M., & Preiss, T. (2012). Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Research, 40, 5023–5033.PubMedPubMedCentralCrossRefGoogle Scholar
  154. Tanabe, A., Tanikawa, K., Tsunetomi, M., Takai, K., Ikeda, H., Konno, J., Torigoe, T., Maeda, H., Kutomi, G., Okita, K., Mori, M., & Sahara, H. (2016). RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1alpha mRNA is translated. Cancer Letters, 376, 34–42.PubMedCrossRefPubMedCentralGoogle Scholar
  155. Tripathi, V., Ellis, J. D., Shen, Z., Song, D. Y., Pan, Q., Watt, A. T., Freier, S. M., Bennett, C. F., Sharma, A., Bubulya, P. A., Blencowe, B. J., Prasanth, S. G., & Prasanth, K. V. (2010). The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Molecular Cell, 39, 925–938.PubMedPubMedCentralCrossRefGoogle Scholar
  156. Tsai, M. C., Manor, O., Wan, Y., Mosammaparast, N., Wang, J. K., Lan, F., Shi, Y., Segal, E., & Chang, H. Y. (2010). Long noncoding RNA as modular scaffold of histone modification complexes. Science, 329, 689–693.PubMedPubMedCentralCrossRefGoogle Scholar
  157. Wang, K. C., & Chang, H. Y. (2011). Molecular mechanisms of long noncoding RNAs. Molecular Cell, 43, 904–914.PubMedPubMedCentralCrossRefGoogle Scholar
  158. Wang, X., Lu, Z., Gomez, A., Hon, G. C., Yue, Y., Han, D., Fu, Y., Parisien, M., Dai, Q., Jia, G., Ren, B., Pan, T., & He, C. (2014a). N6-methyladenosine-dependent regulation of messenger RNA stability. Nature, 505, 117–120.CrossRefGoogle Scholar
  159. Wang, Y., Li, Y., Toth, J. I., Petroski, M. D., Zhang, Z., & Zhao, J. C. (2014b). N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biology, 16, 191–198.PubMedPubMedCentralCrossRefGoogle Scholar
  160. Wang, X., Zhao, B. S., Roundtree, I. A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., & He, C. (2015). N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell, 161, 1388–1399.PubMedPubMedCentralCrossRefGoogle Scholar
  161. Wang, X., Feng, J., Xue, Y., Guan, Z., Zhang, D., Liu, Z., Gong, Z., Wang, Q., Huang, J., Tang, C., Zou, T., & Yin, P. (2016a). Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex. Nature, 534, 575–578.PubMedCrossRefPubMedCentralGoogle Scholar
  162. Wang, P., Doxtader, K. A., & Nam, Y. (2016b). Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Molecular Cell, 63, 306–317.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Warda, A. S., Kretschmer, J., Hackert, P., Lenz, C., Urlaub, H., Hobartner, C., Sloan, K. E., & Bohnsack, M. T. (2017). Human METTL16 is a N(6)-methyladenosine (m(6)A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. EMBO Reports, 18, 2004–2014.PubMedPubMedCentralCrossRefGoogle Scholar
  164. Wei, C. M., & Moss, B. (1977). Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry, 16, 1672–1676.PubMedCrossRefPubMedCentralGoogle Scholar
  165. Wilusz, J. E., Freier, S. M., & Spector, D. L. (2008). 3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell, 135, 919–932.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Winter, J., Jung, S., Keller, S., Gregory, R. I., & Diederichs, S. (2009). Many roads to maturity: MicroRNA biogenesis pathways and their regulation. Nature Cell Biology, 11, 228–234.PubMedCrossRefPubMedCentralGoogle Scholar
  167. Wojtas, M. N., Pandey, R. R., Mendel, M., Homolka, D., Sachidanandam, R., & Pillai, R. S. (2017). Regulation of m(6)A transcripts by the 3′→5′ RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline. Molecular Cell, 68, 374–387.e12.PubMedCrossRefPubMedCentralGoogle Scholar
  168. Wu, L., Zhang, L., & Zheng, S. (2017). Role of the long non-coding RNA HOTAIR in hepatocellular carcinoma. Oncology Letters, 14, 1233–1239.PubMedPubMedCentralCrossRefGoogle Scholar
  169. Wutz, A. (2011). Gene silencing in X-chromosome inactivation: Advances in understanding facultative heterochromatin formation. Nature Reviews Genetics, 12, 542–553.PubMedCrossRefPubMedCentralGoogle Scholar
  170. Wyatt, G. R. (1950). Occurrence of 5-methylcytosine in nucleic acids. Nature, 166, 237–238.PubMedCrossRefPubMedCentralGoogle Scholar
  171. Xiao, W., Adhikari, S., Dahal, U., Chen, Y. S., Hao, Y. J., Sun, B. F., Sun, H. Y., Li, A., Ping, X. L., Lai, W. Y., Wang, X., Ma, H. L., Huang, C. M., Yang, Y., Huang, N., Jiang, G. B., Wang, H. L., Zhou, Q., Wang, X. J., Zhao, Y. L., & Yang, Y. G. (2016). Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Molecular Cell, 61, 507–519.PubMedCrossRefPubMedCentralGoogle Scholar
  172. Xu, S., Kong, D., Chen, Q., Ping, Y., & Pang, D. (2017). Oncogenic long noncoding RNA landscape in breast cancer. Molecular Cancer, 16, 129.PubMedPubMedCentralCrossRefGoogle Scholar
  173. Yamamoto, K., Nagata, K., Kida, A., & Hamaguchi, H. (2002). Acquired gain of an X chromosome as the sole abnormality in the blast crisis of chronic neutrophilic leukemia. Cancer Genetics and Cytogenetics, 134, 84–87.PubMedCrossRefPubMedCentralGoogle Scholar
  174. Yamauchi, Y., Nobe, Y., Izumikawa, K., Higo, D., Yamagishi, Y., Takahashi, N., Nakayama, H., Isobe, T., & Taoka, M. (2016). A mass spectrometry-based method for direct determination of pseudouridine in RNA. Nucleic Acids Research, 44, e59.PubMedCrossRefPubMedCentralGoogle Scholar
  175. Yang, X., Yang, Y., Sun, B. F., Chen, Y. S., Xu, J. W., Lai, W. Y., Li, A., Wang, X., Bhattarai, D. P., Xiao, W., Sun, H. Y., Zhu, Q., Ma, H. L., Adhikari, S., Sun, M., Hao, Y. J., Zhang, B., Huang, C. M., Huang, N., Jiang, G. B., Zhao, Y. L., Wang, H. L., Sun, Y. P., & Yang, Y. G. (2017). 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Research, 27, 606–625.PubMedPubMedCentralCrossRefGoogle Scholar
  176. Yi, J., Gao, R., Chen, Y., Yang, Z., Han, P., Zhang, H., Dou, Y., Liu, W., Wang, W., Du, G., Xu, Y., & Wang, J. (2017). Overexpression of NSUN2 by DNA hypomethylation is associated with metastatic progression in human breast cancer. Oncotarget, 8, 20751–20765.PubMedPubMedCentralGoogle Scholar
  177. Yue, Y., Liu, J., Cui, X., Cao, J., Luo, G., Zhang, Z., Cheng, T., Gao, M., Shu, X., Ma, H., Wang, F., Wang, X., Shen, B., Wang, Y., Feng, X., He, C., & Liu, J. (2018). VIRMA mediates preferential m(6)A mRNA methylation in 3’UTR and near stop codon and associates with alternative polyadenylation. Cell Discovery, 4, 10.PubMedPubMedCentralCrossRefGoogle Scholar
  178. Zaganelli, S., Rebelo-Guiomar, P., Maundrell, K., Rozanska, A., Pierredon, S., Powell, C. A., Jourdain, A. A., Hulo, N., Lightowlers, R. N., Chrzanowska-Lightowlers, Z. M., Minczuk, M., & Martinou, J. C. (2017). The Pseudouridine synthase RPUSD4 is an essential component of mitochondrial RNA granules. The Journal of Biological Chemistry, 292, 4519–4532.PubMedPubMedCentralCrossRefGoogle Scholar
  179. Zhang, B., Arun, G., Mao, Y. S., Lazar, Z., Hung, G., Bhattacharjee, G., Xiao, X., Booth, C. J., Wu, J., Zhang, C., & Spector, D. L. (2012). The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Reports, 2, 111–123.PubMedPubMedCentralCrossRefGoogle Scholar
  180. Zhang, C., Samanta, D., Lu, H., Bullen, J. W., Zhang, H., Chen, I., He, X., & Semenza, G. L. (2016). Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m(6)A-demethylation of NANOG mRNA. Proceedings of the National Academy of Sciences of the United States of America, 113, E2047–E2056.PubMedPubMedCentralCrossRefGoogle Scholar
  181. Zhang, S., Zhao, B. S., Zhou, A., Lin, K., Zheng, S., Lu, Z., Chen, Y., Sulman, E. P., Xie, K., Bogler, O., Majumder, S., He, C., & Huang, S. (2017a). m6A demethylase ALKBH5 maintains Tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell, 31, 591–606.e6.PubMedPubMedCentralCrossRefGoogle Scholar
  182. Zhang, X., Chi, Q., & Zhao, Z. (2017b). Up-regulation of long non-coding RNA SPRY4-IT1 promotes tumor cell migration and invasion in lung adenocarcinoma. Oncotarget, 8, 51058–51065.PubMedPubMedCentralGoogle Scholar
  183. Zhao, X., Patton, J. R., Davis, S. L., Florence, B., Ames, S. J., & Spanjaard, R. A. (2004). Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator. Molecular Cell, 15, 549–558.PubMedCrossRefPubMedCentralGoogle Scholar
  184. Zhao, X., Patton, J. R., Ghosh, S. K., Fischel-Ghodsian, N., Shen, L., & Spanjaard, R. A. (2007). Pus3p- and Pus1p-dependent pseudouridylation of steroid receptor RNA activator controls a functional switch that regulates nuclear receptor signaling. Molecular Endocrinology, 21, 686–699.PubMedCrossRefPubMedCentralGoogle Scholar
  185. Zheng, G., Dahl, J. A., Niu, Y., Fedorcsak, P., Huang, C. M., Li, C. J., Vagbo, C. B., Shi, Y., Wang, W. L., Song, S. H., Lu, Z., Bosmans, R. P., Dai, Q., Hao, Y. J., Yang, X., Zhao, W. M., Tong, W. M., Wang, X. J., Bogdan, F., Furu, K., Fu, Y., Jia, G., Zhao, X., Liu, J., Krokan, H. E., Klungland, A., Yang, Y. G., & He, C. (2013). ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Molecular Cell, 49, 18–29.PubMedCrossRefPubMedCentralGoogle Scholar
  186. Zhou, J., Wan, J., Gao, X., Zhang, X., Jaffrey, S. R., & Qian, S. B. (2015). Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature, 526, 591–594.PubMedPubMedCentralCrossRefGoogle Scholar
  187. Zhou, K. I., Parisien, M., Dai, Q., Liu, N., Diatchenko, L., Sachleben, J. R., & Pan, T. (2016). N(6)-Methyladenosine modification in a long noncoding RNA hairpin predisposes its conformation to protein binding. Journal of Molecular Biology, 428, 822–833.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Medicine, Martin-Luther-University Halle-WittenbergHalle (Saale)Germany

Personalised recommendations