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Stem Cell Reviews and Reports

, Volume 15, Issue 4, pp 474–496 | Cite as

Deciphering the Epitranscriptomic Signatures in Cell Fate Determination and Development

  • Varun Haran
  • Nibedita LenkaEmail author
Article

Abstract

Precise regulation of transcriptome modulates several vital aspects in an organism that includes gene expression, cellular activities and development, and its perturbation ensuing pathological conditions. Around 150 post-transcriptional modifications of RNA have been identified till date, which are evolutionarily conserved and likewise prevalent across RNA classes including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and detected less frequently in small nuclear RNA (snRNA) and microRNAs (miRNA). Among the RNA modifications documented, N6-methyladenosine (m6A) is the best characterised till date. Also, N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine (Ψ) are some of the other prominent modifications detected in coding and non-coding RNAs. “Epitranscriptome”, ensemble of these post-transcriptional RNA modifications, precisely coordinates gene expression and biological processes. Current literatures suggest the critical involvement of epitranscriptomics in several organisms during early development, contributing to cell fate specification and physiology. Indeed, epitranscriptomics similar to DNA epigenetics involves combinatorial dynamics provided by modified RNA molecules and associated protein complexes, which function as “writers”, “erasers” and “readers” of these modifications. A novel code orchestrating gene expression during cell fate determination is generated by the coordinated effects of different classes of modified RNAs and its regulator proteins. In this review, we summarize the current knowhow on N6-methyladenosine (m6A), 5-methylcytosine (m5C) and pseudouridine (ψ) modifications in RNA, the associated regulator proteins and enumerate how the epitranscriptomic regulations are involved in cell fate determination.

Keywords

Epitranscriptomics Post-transcriptional modification RNA binding protein Embryonic development Stem cells Cell fate 

Notes

Acknowledgements

The work was supported by intramural funding from NCCS to NL and VH is a graduate student supported by fellowship from Council of Scientific and Industrial Research (CSIR), India.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

References

  1. 1.
    Li, S., & Mason, C. E. (2014). The pivotal regulatory landscape of RNA modifications. Annual Review of Genomics and Human Genetics, 15, 127–150.Google Scholar
  2. 2.
    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(6), 365–372.Google Scholar
  3. 3.
    Helm, M., & Motorin, Y. (2017). Detecting RNA modifications in the epitranscriptome: Predict and validate. Nature Reviews Genetics, 18(5), 275–291.Google Scholar
  4. 4.
    Cohn, W. E., & Volkin, E. (1951). Nucleoside-5′-phosphates from ribonucleic acid. Nature, 167, 483–484.Google Scholar
  5. 5.
    Roundtree, I. A., Evans, M. E., Pan, T., & He, C. (2017). Dynamic RNA modifications in gene expression regulation. Cell, 169(7), 1187–1200.Google Scholar
  6. 6.
    Schaefer, M., Pollex, T., Hanna, K., Tuorto, F., Meusburger, M., Helm, M., & Lyko, F. (2010). RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes and Development, 24(15), 1590–1595.Google Scholar
  7. 7.
    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(2), 255–261.Google Scholar
  8. 8.
    Peifer, C., Sharma, S., Watzinger, P., Lamberth, S., Kötter, P., & Entian, K. D. (2013). Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA. Nucleic Acids Research, 41(2), 1151–1163.Google Scholar
  9. 9.
    Guy, M. P., & Phizicky, E. M. (2014). Two-subunit enzymes involved in eukaryotic post-transcriptional tRNA modification. RNA Biology, 11(12), 1608–1618.Google Scholar
  10. 10.
    Oerum, S., Dégut, C., Barraud, P., & Tisné, C. (2017). m1A post-transcriptional modification in tRNAs. Biomolecules, 7(1), 20.Google Scholar
  11. 11.
    Dominissini, D., Nachtergaele, S., Moshitch-Moshkovitz, S., Peer, E., Kol, N., Ben-Haim, M. S., Dai, Q., Di Segni, A., Salmon-Divon, M., & Clark, W. C. (2016). The dynamic N 1-methyladenosine methylome in eukaryotic messenger RNA. Nature, 530(7591), 441–446.Google Scholar
  12. 12.
    Li, X., Xiong, X., Wang, K., Wang, L., Shu, X., Ma, S., & Yi, C. (2016). Transcriptome-wide mapping reveals reversible and dynamic N 1-methyladenosine methylome. Nature Chemical Biology, 12(5), 311–316.Google Scholar
  13. 13.
    Zhao, B. S., Roundtree, I. A., & He, C. (2017). Post-transcriptional gene regulation by mRNA modifications. Nature Reviews Molecular Cell Biology, 18(1), 31–42.Google Scholar
  14. 14.
    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(7), 1635–1646.Google Scholar
  15. 15.
    Batista, P. J., Molinie, B., Wang, J., Qu, K., Zhang, J., Li, L., Bouley, D. M., Lujan, E., Haddad, B., Daneshvar, K., Carter, A. C., Flynn, R. A., Zhou, C., Lim, K. S., Dedon, P., Wernig, M. A., Mullen, C., Xing, Y., Giallourakis, C. C., & Chang, H. Y. (2014). M(6)a RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell, 15(6), 707–719.Google Scholar
  16. 16.
    Liu, N., & Pan, T. (2016). N 6-methyladenosine–encoded epitranscriptomics. Nature Structural & Molecular Biology, 23(2), 98–102.Google Scholar
  17. 17.
    Hsu, P. J., Shi, H., & He, C. (2017). Epitranscriptomic influences on development and disease. Genome Biology, 18(1), 197.Google Scholar
  18. 18.
    Dunin-Horkawicz, S., Czerwoniec, A., Gajda, M. J., Feder, M., Grosjean, H., & Bujnicki, J. M. (2006). MODOMICS: A database of RNA modification pathways. Nucleic Acids Research, 34, D145–D149.Google Scholar
  19. 19.
    Boccaletto, P., Machnicka, M. A., Purta, E., Piatkowski, P., Baginski, B., Wirecki, T. K., de Crecy-Lagard, V., Ross, R., Limbach, P. A., Kotter, A., Helm, M., & Bujnicki, J. M. (2018). MODOMICS: A database of RNA modification pathways. 2017 update. Nucleic Acids Research, 46(D1), D303–D307.Google Scholar
  20. 20.
    Sanchez-Vasquez, E., Alata Jimenez, N., Vazquez, N. A., & Strobl-Mazzulla, P. H. (2018). Emerging role of dynamic RNA modifications during animal development. Mechanisms of Development, 154, 24–32.Google Scholar
  21. 21.
    Dubin, D. T., & Taylor, R. H. (1975). The methylation state of poly A-containing-messenger RNA from cultured hamster cells. Nucleic Acids Research, 2(10), 1653–1668.Google Scholar
  22. 22.
    Peer, E., Rechavi, G., & Dominissini, D. (2017). Epitranscriptomics: Regulation of mRNA metabolism through modifications. Current Opinion in Chemical Biology, 41, 93–98.Google Scholar
  23. 23.
    Angelova, M. T., Dimitrova, D. G., Dinges, N., Lence, T., Worpenberg, L., Carre, C., & Roignant, J. Y. (2018). The emerging field of Epitranscriptomics in neurodevelopmental and neuronal disorders. Frontiers in Bioengineering and Biotechnology, 6, 46.Google Scholar
  24. 24.
    Gilbert, W. V., Bell, T. A., & Schaening, C. (2016). Messenger RNA modifications: Form, distribution, and function. Science, 352(6292), 1408–1412.Google Scholar
  25. 25.
    Fustin, J. M., Doi, M., Yamaguchi, Y., Hida, H., Nishimura, S., Yoshida, M., Isagawa, T., Morioka, M. S., Kakeya, H., & Manabe, I. (2013). RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell, 155(4), 793–806.Google Scholar
  26. 26.
    Wang, X., Zhao, B. S., Roundtree, I. A., Lu, Z., Han, D., Ma, H., Weng, X., Chen, K., Shi, H., & He, C. (2015). N6-methyladenosine modulates messenger RNA translation efficiency. Cell, 161(6), 1388–1399.Google Scholar
  27. 27.
    Hubstenberger, A., Courel, M., Bénard, M., Souquere, S., Ernoult-Lange, M., Chouaib, R., Yi, Z., Morlot, J. B., Munier, A., & Fradet, M. (2017). P-body purification reveals the condensation of repressed mRNA regulons. Molecular Cell, 68(1), 144–157.Google Scholar
  28. 28.
    Yang, Y., Hsu, P. J., Chen, Y. S., & Yang, Y. G. (2018). Dynamic transcriptomic m6A decoration: Writers, erasers, readers and functions in RNA metabolism. Cell Research, 28(6), 616–624.Google Scholar
  29. 29.
    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(11), 1233–1247.Google Scholar
  30. 30.
    Zhao, B. S., Wang, X., Beadell, A. V., Lu, Z., Shi, H., Kuuspalu, A., Ho, R. K., & He, C. (2017). M(6)A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature, 542(7642), 475–478.Google Scholar
  31. 31.
    Chang, M., Lv, H., Zhang, W., Ma, C., He, X., Zhao, S., Zhang, Z. W., Zeng, Y. X., Song, S., Niu, Y., & Tong, W. M. (2017). Region-specific RNA m(6)a methylation represents a new layer of control in the gene regulatory network in the mouse brain. Open Biology, 7(9), 170166.Google Scholar
  32. 32.
    Li, M., Zhao, X., Wang, W., Shi, H., Pan, Q., Lu, Z., Perez, S. P., Suganthan, R., He, C., Bjoras, M., & Klungland, A. (2018). Ythdf2-mediated m(6)a mRNA clearance modulates neural development in mice. Genome Biology, 19(1), 69.Google Scholar
  33. 33.
    Yoon, K. J., Ringeling, F. R., Vissers, C., Jacob, F., Pokrass, M., Jimenez-Cyrus, D., Su, Y., Kim, N. S., Zhu, Y., Zheng, L., Kim, S., Wang, X., Dore, L. C., Jin, P., Regot, S., Zhuang, X., Canzar, S., He, C., Ming, G. L., & Song, H. (2017). Temporal control of mammalian cortical neurogenesis by m(6)a methylation. Cell, 171(4), 877–889.Google Scholar
  34. 34.
    Ma, C., Chang, M., Lv, H., Zhang, Z. W., Zhang, W., He, X., Wu, G., Zhao, S., Zhang, Y., Wang, D., Teng, X., Liu, C., Li, Q., Klungland, A., Niu, Y., Song, S., & Tong, W. M. (2018). RNA m(6)a methylation participates in regulation of postnatal development of the mouse cerebellum. Genome Biology, 19(1), 68.Google Scholar
  35. 35.
    Wang, C. X., Cui, G. S., Liu, X., Xu, K., Wang, M., Zhang, X. X., Jiang, L. Y., Li, A., Yang, Y., Lai, W. Y., Sun, B. F., Jiang, G. B., Wang, H. L., Tong, W. M., Li, W., Wang, X. J., Yang, Y. G., & Zhou, Q. (2018). METTL3-mediated m6A modification is required for cerebellar development. PLoS Biology, 16(6), e2004880.Google Scholar
  36. 36.
    Wang, Y., Li, Y., Yue, M., Wang, J., Kumar, S., Wechsler-Reya, R. J., Zhang, Z., Ogawa, Y., Kellis, M., Duester, G., & Zhao, J. C. (2018). N(6)-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications. Nature Neuroscience, 21(2), 195–206.Google Scholar
  37. 37.
    Li, L., Zang, L., Zhang, F., Chen, J., Shen, H., Shu, L., Liang, F., Feng, C., Chen, D., Tao, H., Xu, T., Li, Z., Kang, Y., Wu, H., Tang, L., Zhang, P., Jin, P., Shu, Q., & Li, X. (2017). Fat mass and obesity-associated (FTO) protein regulates adult neurogenesis. Human Molecular Genetics, 26(13), 2398–2411.Google Scholar
  38. 38.
    Kimelman, D. (2006). Mesoderm induction: From caps to chips. Nature Reviews. Genetics, 7(5), 360–372.Google Scholar
  39. 39.
    Zhang, C., Chen, Y., Sun, B., Wang, L., Yang, Y., Ma, D., Lv, J., Heng, J., Ding, Y., Xue, Y., Lu, X., Xiao, W., Yang, Y. G., & Liu, F. (2017). M(6)a modulates haematopoietic stem and progenitor cell specification. Nature, 549(7671), 273–276.Google Scholar
  40. 40.
    Vu, L. P., Pickering, B. F., Cheng, Y., Zaccara, S., Nguyen, D., Minuesa, G., Chou, T., Chow, A., Saletore, Y., MacKay, M., Schulman, J., Famulare, C., Patel, M., Klimek, V. M., Garrett-Bakelman, F. E., Melnick, A., Carroll, M., Mason, C. E., Jaffrey, S. R., & Kharas, M. G. (2017). The N(6)-methyladenosine (m(6)a)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells. Nature Medicine, 23(11), 1369–1376.Google Scholar
  41. 41.
    Kudou, K., Komatsu, T., Nogami, J., Maehara, K., Harada, A., Saeki, H., Oki, E., Maehara, Y., & Ohkawa, Y. (2017). The requirement of Mettl3-promoted MyoD mRNA maintenance in proliferative myoblasts for skeletal muscle differentiation. Open Biology, 7(9), 170119.Google Scholar
  42. 42.
    Ben-Haim, M. S., Moshitch-Moshkovitz, S., & Rechavi, G. (2015). FTO: Linking m6A demethylation to adipogenesis. Cell Research, 25(1), 3–4.Google Scholar
  43. 43.
    Zhao, X., Yang, Y., Sun, B. F., Shi, Y., Yang, X., Xiao, W., Hao, Y. J., Ping, X. L., Chen, Y. S., Wang, W. J., Jin, K. X., Wang, X., Huang, C. M., Fu, Y., Ge, X. M., Song, S. H., Jeong, H. S., Yanagisawa, H., Niu, Y., Jia, G. F., Wu, W., Tong, W. M., Okamoto, A., He, C., Rendtlew-Danielsen, J. M., Wang, X. J., & Yang, Y. G. (2014). FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Research, 24(12), 1403–1419.Google Scholar
  44. 44.
    Kobayashi, M., Ohsugi, M., Sasako, T., Awazawa, M., Umehara, T., Iwane, A., Kobayashi, N., Okazaki, Y., Kubota, N., Suzuki, R., Waki, H., Horiuchi, K., Hamakubo, T., Kodama, T., Aoe, S., Tobe, K., Kadowaki, T., & Ueki, K. (2018). The RNA methyltransferase complex of WTAP, METTL3, and METTL14 regulates mitotic clonal expansion in Adipogenesis. Molecular and Cellular Biology, 38(16), e00116–e00118.Google Scholar
  45. 45.
    Hsu, P. J., Zhu, Y., Ma, H., Guo, Y., Shi, X., Liu, Y., Qi, M., Lu, Z., Shi, H., Wang, J., Cheng, Y., Luo, G., Dai, Q., Liu, M., Guo, X., Sha, J., Shen, B., & He, C. (2017). Ythdc2 is an N(6)-methyladenosine binding protein that regulates mammalian spermatogenesis. Cell Research, 27(9), 1115–1127.Google Scholar
  46. 46.
    Kasowitz, S. D., Ma, J., Anderson, S. J., Leu, N. A., Xu, Y., Gregory, B. D., Schultz, R. M., & Wang, P. J. (2018). Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLoS Genetics, 14(5), e1007412.Google Scholar
  47. 47.
    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(1), 18–29.Google Scholar
  48. 48.
    Lin, Z., Hsu, P. J., Xing, X., Fang, J., Lu, Z., Zou, Q., Zhang, K. J., Zhang, X., Zhou, Y., Zhang, T., Zhang, Y., Song, W., Jia, G., Yang, X., He, C., & Tong, M. H. (2017). Mettl3−/Mettl14-mediated mRNA N(6)-methyladenosine modulates murine spermatogenesis. Cell Research, 27(10), 1216–1230.Google Scholar
  49. 49.
    Geula, S., Moshitch-Moshkovitz, S., Dominissini, D., Mansour, A. A., Kol, N., Salmon-Divon, M., Hershkovitz, V., Peer, E., Mor, N., Manor, Y. S., Ben-Haim, M. S., Eyal, E., Yunger, S., Pinto, Y., Jaitin, D. A., Viukov, S., Rais, Y., Krupalnik, V., Chomsky, E., Zerbib, M., Maza, I., Rechavi, Y., Massarwa, R., Hanna, S., Amit, I., Levanon, E. Y., Amariglio, N., Stern-Ginossar, N., Novershtern, N., Rechavi, G., & Hanna, J. H. (2015). Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science, 347(6225), 1002–1006.Google Scholar
  50. 50.
    Lin, S., & Gregory, R. I. (2014). Methyltransferases modulate RNA stability in embryonic stem cells. Nature Cell Biology, 16(2), 129–131.Google Scholar
  51. 51.
    Wang, Y., Li, Y., Toth, J. I., Petroski, M. D., Zhang, Z., & Zhao, J. C. (2014). N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nature Cell Biology, 16(2), 191–198.Google Scholar
  52. 52.
    Aguilo, F., Zhang, F., Sancho, A., Fidalgo, M., Di Cecilia, S., Vashisht, A., Lee, D. F., Chen, C. H., Rengasamy, M., Andino, B., Jahouh, F., Roman, A., Krig, S. R., Wang, R., Zhang, W., Wohlschlegel, J. A., Wang, J., & Walsh, M. J. (2015). Coordination of m(6)a mRNA methylation and gene transcription by ZFP217 regulates pluripotency and reprogramming. Cell Stem Cell, 17(6), 689–704.Google Scholar
  53. 53.
    Chen, T., Hao, Y. J., Zhang, Y., Li, M. M., Wang, M., Han, W., Wu, Y., Lv, Y., Hao, J., Wang, L., Li, A., Yang, Y., Jin, K. X., Zhao, X., Li, Y., Ping, X. L., Lai, W. Y., Wu, L. G., Jiang, G., Wang, H. L., Sang, L., Wang, X. J., Yang, Y. G., & Zhou, Q. (2015). M(6)a RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell, 16(3), 289–301.Google Scholar
  54. 54.
    Wen, J., Lv, R., Ma, H., Shen, H., He, C., Wang, J., Jiao, F., Liu, H., Yang, P., Tan, L., Lan, F., Shi, Y. G., He, C., Shi, Y., & Diao, J. (2018). Zc3h13 regulates nuclear RNA m(6)a methylation and mouse embryonic stem cell self-renewal. Molecular Cell, 69(6), 1028–1038.Google Scholar
  55. 55.
    Bertero, A., Brown, S., Madrigal, P., Osnato, A., Ortmann, D., Yiangou, L., Kadiwala, J., Hubner, N. C., de Los Mozos, I. R., Sadee, C., Lenaerts, A. S., Nakanoh, S., Grandy, R., Farnell, E., Ule, J., Stunnenberg, H. G., Mendjan, S., & Vallier, L. (2018). The SMAD2/3 interactome reveals that TGFbeta controls m(6)a mRNA methylation in pluripotency. Nature, 555(7695), 256–259.Google Scholar
  56. 56.
    Verma, M. K., & Lenka, N. (2010). Temporal and contextual orchestration of cardiac fate by WNT-BMP synergy and threshold. Journal of Cellular and Molecular Medicine, 14(8), 2094–2108.Google Scholar
  57. 57.
    Faulds, K. J., Egelston, J. N., Sedivy, L. J., Mitchell, M. K., Garimella, S., Kozlowski, H., D'Alessandro, A., Hansen, K. C., Balsbaugh, J. L., & Phiel, C. J. (2018). Glycogen synthase kinase-3 (Gsk-3) activity regulates mRNA methylation in mouse embryonic stem cells. The Journal of Biological Chemistry, 293(27), 10731–10743.Google Scholar
  58. 58.
    Yang, D., Qiao, J., Wang, G., Lan, Y., Li, G., Guo, X., Xi, J., Ye, D., Zhu, S., Chen, W., Jia, W., Leng, Y., Wan, X., & Kang, J. (2018). N6-Methyladenosine modification of lincRNA 1281 is critically required for mESC differentiation potential. Nucleic Acids Research, 46(8), 3906–3920.Google Scholar
  59. 59.
    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, 71(10), 3971–3975.Google Scholar
  60. 60.
    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(11), 5023–5033.Google Scholar
  61. 61.
    Khoddami, V., & Cairns, B. R. (2013). Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nature Biotechnology, 31(5), 458–464.Google Scholar
  62. 62.
    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 m(5)C reader. Cell Research, 27(5), 606–625.Google Scholar
  63. 63.
    Fu, L., Guerrero, C. R., Zhong, N., Amato, N. J., Liu, Y., Liu, S., Cai, Q., Ji, D., Jin, S. G., Niedernhofer, L. J., Pfeifer, G. P., Xu, G. L., & Wang, Y. (2014). Tet-mediated formation of 5-hydroxymethylcytosine in RNA. Journal of the American Chemical Society, 136(33), 11582–11585.Google Scholar
  64. 64.
    Delatte, B., Wang, F., Ngoc, L. V., Collignon, E., Bonvin, E., Deplus, R., Calonne, E., Hassabi, B., Putmans, P., Awe, S., Wetzel, C., Kreher, J., Soin, R., Creppe, C., Limbach, P. A., Gueydan, C., Kruys, V., Brehm, A., Minakhina, S., Defrance, M., Steward, R., & Fuks, F. (2016). RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science, 351(6270), 282–285.Google Scholar
  65. 65.
    Guallar, D., Bi, X., Pardavila, J. A., Huang, X., Saenz, C., Shi, X., Zhou, H., Faiola, F., Ding, J., Haruehanroengra, P., Yang, F., Li, D., Sanchez-Priego, C., Saunders, A., Pan, F., Valdes, V. J., Kelley, K., Blanco, M. G., Chen, L., Wang, H., Sheng, J., Xu, M., Fidalgo, M., Shen, X., & Wang, J. (2018). RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells. Nature Genetics, 50(3), 443–451.Google Scholar
  66. 66.
    Trixl, L., Amort, T., Wille, A., Zinni, M., Ebner, S., Hechenberger, C., Eichin, F., Gabriel, H., Schoberleitner, I., Huang, A., Piatti, P., Nat, R., Troppmair, J., & Lusser, A. (2018). RNA cytosine methyltransferase Nsun3 regulates embryonic stem cell differentiation by promoting mitochondrial activity. Cellular and Molecular Life Sciences, 75(8), 1483–1497.Google Scholar
  67. 67.
    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), 1.Google Scholar
  68. 68.
    Miao, Z., Xin, N., Wei, B., Hua, X., Zhang, G., Leng, C., Zhao, C., Wu, D., Li, J., Ge, W., Sun, M., & Xu, X. (2016). 5-hydroxymethylcytosine is detected in RNA from mouse brain tissues. Brain Research, 1642, 546–552.Google Scholar
  69. 69.
    Flores, J. V., Cordero-Espinoza, L., Oeztuerk-Winder, F., Andersson-Rolf, A., Selmi, T., Blanco, S., Tailor, J., Dietmann, S., & Frye, M. (2017). Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility. Stem Cell Reports, 8(1), 112–124.Google Scholar
  70. 70.
    Blanco, S., Dietmann, S., Flores, J. V., Hussain, S., Kutter, C., Humphreys, P., Lukk, M., Lombard, P., Treps, L., Popis, M., Kellner, S., Holter, S. M., Garrett, L., Wurst, W., Becker, L., Klopstock, T., Fuchs, H., Gailus-Durner, V., Hrabe de Angelis, M., Karadottir, R. T., Helm, M., Ule, J., Gleeson, J. G., Odom, D. T., & Frye, M. (2014). Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. The EMBO Journal, 33(18), 2020–2039.Google Scholar
  71. 71.
    Cohn, W. E. (1960). Pseudouridine, a carbon-carbon linked ribonucleoside in ribonucleic acids: Isolation, structure, and chemical characteristics. The Journal of Biological Chemistry, 235, 1488–1498.Google Scholar
  72. 72.
    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(8), 592–597.Google Scholar
  73. 73.
    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. (2014). Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell, 159(1), 148–162.Google Scholar
  74. 74.
    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(7525), 143–146.Google Scholar
  75. 75.
    Guzzi, N., Ciesla, M., Ngoc, P. C. T., Lang, S., Arora, S., Dimitriou, M., Pimkova, K., Sommarin, M. N. E., Munita, R., Lubas, M., Lim, Y., Okuyama, K., Soneji, S., Karlsson, G., Hansson, J., Jonsson, G., Lund, A. H., Sigvardsson, M., Hellstrom-Lindberg, E., Hsieh, A. C., & Bellodi, C. (2018). Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell, 173(5), 1204–1216.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.National Centre for Cell ScienceS. P. Pune University CampusPuneIndia

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