RNA Methylation in the Control of Stem Cell Activity and Epidermal Differentiation

  • Abdulrahim A. Sajini
  • Michaela FryeEmail author
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


Abundant non-coding RNAs including transfer and ribosomal RNAs are extensively modified, and some of these chemical modifications such as methylation also occur in regulatory non-coding RNAs and coding RNAs. The deposition of a methyl mark onto adenosines (m6A) and cytosines (m5C) is highly conserved and both have emerged as important modifications regulating fundamental cellular processes in developing and adult tissues in mammals. In this chapter, we will review the broad roles of m6A and m5C post-transcriptional methylation in regulating stem cell fate and differentiation processes in skin and other adult tissues, and we will discuss the existence of an additional layer of protein expression control through epigenetic regulation at the RNA level.



The authors thank members of the Frye Laboratory for helpful discussion. M.F. is supported by grants from Cancer Research UK (CR-UK), the European Research Council (ERC), the Medical Research Council (MRC), and Worldwide Cancer Research (WCR). A.S. was funded by a scholarship from the University of Tabuk, Saudi Arabia.


  1. 1.
    Lopez-Pajares V, et al. Genetic pathways in disorders of epidermal differentiation. Trends Genet. 2013;29(1):31–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Hsu YC, Li L, Fuchs E. Emerging interactions between skin stem cells and their niches. Nat Med. 2014;20(8):847–56.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Frye M, Benitah SA. Chromatin regulators in mammalian epidermis. Semin Cell Dev Biol. 2012;23(8):897–905.PubMedCrossRefGoogle Scholar
  4. 4.
    Botchkarev VA. Epigenetic regulation of epidermal development and keratinocyte differentiation. J Investig Dermatol Symp Proc. 2015;17(1):18–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Perdigoto CN, et al. Epigenetic regulation of epidermal differentiation. Cold Spring Harb Perspect Med. 2014;4(2):1–19.Google Scholar
  6. 6.
    Machnicka MA, et al. MODOMICS: a database of RNA modification pathways--2013 update. Nucleic Acids Res. 2013;41(Database issue):D262–7.PubMedGoogle Scholar
  7. 7.
    Cantara WA, et al. The RNA modification database, RNAMDB: 2011 update. Nucleic Acids Res. 2011;39(Database issue):D195–201.PubMedCrossRefGoogle Scholar
  8. 8.
    Helm M, Alfonzo JD. Posttranscriptional RNA modifications: playing metabolic games in a cell’s chemical Legoland. Chem Biol. 2014;21(2):174–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Torres AG, Batlle E, Ribas de Pouplana L. Role of tRNA modifications in human diseases. Trends Mol Med. 2014;20:306.PubMedCrossRefGoogle Scholar
  10. 10.
    Blanco S, Frye M. Role of RNA methyltransferases in tissue renewal and pathology. Curr Opin Cell Biol. 2014;31C:1–7.CrossRefGoogle Scholar
  11. 11.
    Powell CA, Nicholls TJ, Minczuk M. Nuclear-encoded factors involved in post-transcriptional processing and modification of mitochondrial tRNAs in human disease. Front Genet. 2015;6:79.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Li S, Mason CE. The pivotal regulatory landscape of RNA modifications. Annu Rev Genomics Hum Genet. 2014;15:127–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Towns WL, Begley TJ. Transfer RNA methytransferases and their corresponding modifications in budding yeast and humans: activities, predications, and potential roles in human health. DNA Cell Biol. 2012;31(4):434–54.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Bujnicki JM, et al. Sequence-structure-function studies of tRNA:m5C methyltransferase Trm4p and its relationship to DNA:m5C and RNA:m5U methyltransferases. Nucleic Acids Res. 2004;32(8):2453–63.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Motorin Y, Lyko F, Helm M. 5-methylcytosine in RNA: detection, enzymatic formation and biological functions. Nucleic Acids Res. 2010;38(5):1415–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Burgess AL, David R, Searle IR. Conservation of tRNA and rRNA 5-methylcytosine in the kingdom Plantae. BMC Plant Biol. 2015;15:199.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Dominissini D, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485(7397):201–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Meyer KD, et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell. 2012;149(7):1635–46.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Hussain S, et al. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep. 2013;4(2):255–61.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Squires JE, et al. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 2012;40(11):5023–33.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Khoddami V, Cairns BR. Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat Biotechnol. 2013;31(5):458–64.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A. 1974;71(10):3971–5.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Perry RP, et al. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5′ terminus. Cell. 1975;4(4):387–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Rottman F, Shatkin AJ, Perry RP. Sequences containing methylated nucleotides at the 5′ termini of messenger RNAs: possible implications for processing. Cell. 1974;3(3):197–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Narayan P, Rottman FM. An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science. 1988;242(4882):1159–62.PubMedCrossRefGoogle Scholar
  26. 26.
    Csepany T, et al. Sequence specificity of mRNA N6-adenosine methyltransferase. J Biol Chem. 1990;265(33):20117–22.PubMedGoogle Scholar
  27. 27.
    Rottman FM, et al. N6-adenosine methylation in mRNA: substrate specificity and enzyme complexity. Biochimie. 1994;76(12):1109–14.PubMedCrossRefGoogle Scholar
  28. 28.
    Dubin DT, Taylor RH. The methylation state of poly A-containing messenger RNA from cultured hamster cells. Nucleic Acids Res. 1975;2(10):1653–68.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Maden BE. Locations of methyl groups in 28 S rRNA of Xenopus laevis and man. Clustering in the conserved core of molecule. J Mol Biol. 1988;201(2):289–314.PubMedCrossRefGoogle Scholar
  30. 30.
    Gambaryan AS, Venkstern TV, Bayev AA. On the mechanism of tRNA methylase-tRNA recognition. Nucleic Acids Res. 1976;3(8):2079–87.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Schaefer M, et al. RNA cytosine methylation analysis by bisulfite sequencing. Nucleic Acids Res. 2009;37(2):e12.PubMedCrossRefGoogle Scholar
  32. 32.
    Blanco S, et al. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. 2014;33(18):2020–39.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Edelheit S, et al. Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m(5)C within archaeal mRNAs. PLoS Genet. 2013;9(6):e1003602.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hussain S, et al. Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol. 2013;14(11):215.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Alarcon CR, et al. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015;519(7544):482–5.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Geula S, et al. Stem cells. m6A mRNA methylation facilitates resolution of naive pluripotency toward differentiation. Science. 2015;347(6225):1002–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Yue Y, Liu J, He C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015;29(13):1343–55.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Ke S, et al. m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev. 2017;31(10):990–1006.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Linder B, et al. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods. 2015;12(8):767–72.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Liu N, Pan T. Probing N(6)-methyladenosine (m(6)a) RNA modification in total RNA with SCARLET. Methods Mol Biol. 2016;1358:285–92.PubMedCrossRefGoogle Scholar
  41. 41.
    King MY, Redman KL. RNA methyltransferases utilize two cysteine residues in the formation of 5-methylcytosine. Biochemistry. 2002;41(37):11218–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Sugimoto Y, et al. Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions. Genome Biol. 2012;13(8):R67.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Liu Y, Santi DV. m5C RNA and m5C DNA methyl transferases use different cysteine residues as catalysts. Proc Natl Acad Sci U S A. 2000;97(15):8263–5.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Redman KL. Assembly of protein-RNA complexes using natural RNA and mutant forms of an RNA cytosine methyltransferase. Biomacromolecules. 2006;7(12):3321–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Frye M, Blanco S. Post-transcriptional modifications in development and stem cells. Development. 2016;143(21):3871–81.PubMedCrossRefGoogle Scholar
  46. 46.
    Haag S, et al. NSUN6 is a human RNA methyltransferase that catalyzes formation of m5C72 in specific tRNAs. RNA. 2015;21:1532.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Tuorto F, et al. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012;19(9):900–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Goll MG, et al. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science. 2006;311(5759):395–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Van Haute L, et al. Deficient methylation and formylation of mt-tRNA(met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016;7:12039.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Blanco S, et al. Stem cell function and stress response are controlled by protein synthesis. Nature. 2016;534(7607):335–40.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Flores JV, et al. Cytosine-5 RNA methylation regulates neural stem cell differentiation and motility. Stem Cell Reports. 2017;8(1):112–24.PubMedCrossRefGoogle Scholar
  52. 52.
    Schaefer M, et al. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 2010;24(15):1590–5.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Fu H, et al. Stress induces tRNA cleavage by angiogenin in mammalian cells. FEBS Lett. 2009;583(2):437–42.PubMedCrossRefGoogle Scholar
  54. 54.
    Ivanov P, et al. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011;43(4):613–23.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Spriggs KA, Bushell M, Willis AE. Translational regulation of gene expression during conditions of cell stress. Mol Cell. 2010;40(2):228–37.PubMedCrossRefGoogle Scholar
  56. 56.
    Sobala A, Hutvagner G. Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells. RNA Biol. 2013;10(4):553–63.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Gebetsberger J, et al. tRNA-derived fragments target the ribosome and function as regulatory non-coding RNA in Haloferax volcanii. Archaea. 2012;2012:260909.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Tuorto F, et al. The tRNA methyltransferase Dnmt2 is required for accurate polypeptide synthesis during haematopoiesis. EMBO J. 2015;34:2350.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Warren L, et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell. 2010;7(5):618–30.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Zhang X, et al. The tRNA methyltransferase NSun2 stabilizes p16INK(4) mRNA by methylating the 3′-untranslated region of p16. Nat Commun. 2012;3:712.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Haag S, et al. NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon recognition in mitochondrial translation. EMBO J. 2016;35:2104.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Nakano S, et al. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNA(Met). Nat Chem Biol. 2016;12(7):546–51.PubMedCrossRefGoogle Scholar
  63. 63.
    Metodiev MD, et al. NSUN4 is a dual function mitochondrial protein required for both methylation of 12S rRNA and coordination of mitoribosomal assembly. PLoS Genet. 2014;10(2):e1004110.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Spahr H, et al. Structure of the human MTERF4-NSUN4 protein complex that regulates mitochondrial ribosome biogenesis. Proc Natl Acad Sci U S A. 2012;109(38):15253–8.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Yakubovskaya E, et al. Structure of the essential MTERF4:NSUN4 protein complex reveals how an MTERF protein collaborates to facilitate rRNA modification. Structure. 2012;20(11):1940–7.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Schosserer M, et al. Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat Commun. 2015;6:6158.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Sharma S, et al. Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 2013;41(10):5428–43.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Bourgeois G, et al. Eukaryotic rRNA modification by yeast 5-Methylcytosine-Methyltransferases and human proliferation-associated antigen p120. PLoS One. 2015;10(7):e0133321.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Jhiang SM, Yaneva M, Busch H. Expression of human proliferation-associated nucleolar antigen p120. Cell Growth Differ. 1990;1(7):319–24.PubMedGoogle Scholar
  70. 70.
    Aguilo F, et al. Deposition of 5-Methylcytosine on enhancer RNAs enables the Coactivator function of PGC-1alpha. Cell Rep. 2016;14(3):479–92.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Harris T, et al. 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. Biol Reprod. 2007;77(2):376–82.PubMedCrossRefGoogle Scholar
  72. 72.
    Khosronezhad N, Colagar AH, Jorsarayi SG. T26248G-transversion mutation in exon7 of the putative methyltransferase Nsun7 gene causes a change in protein folding associated with reduced sperm motility in asthenospermic men. Reprod Fertil Dev. 2015;27:471–80.PubMedCrossRefGoogle Scholar
  73. 73.
    Wei CM, Gershowitz A, Moss B. Methylated nucleotides block 5′ terminus of HeLa cell messenger RNA. Cell. 1975;4(4):379–86.PubMedCrossRefGoogle Scholar
  74. 74.
    Ping XL, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014;24(2):177–89.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Wang Y, et al. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol. 2014;16(2):191–8.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Liu J, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014;10(2):93–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Chen T, et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 2015;16(3):289–301.PubMedCrossRefGoogle Scholar
  78. 78.
    Jia G, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7(12):885–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Zheng G, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2013;49(1):18–29.PubMedCrossRefGoogle Scholar
  80. 80.
    Fischer J, et al. Inactivation of the Fto gene protects from obesity. Nature. 2009;458(7240):894–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Boissel S, et al. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet. 2009;85(1):106–11.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Wang X, et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 2014;505(7481):117–20.PubMedCrossRefGoogle Scholar
  83. 83.
    Xu C, et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol. 2014;10(11):927–9.PubMedCrossRefGoogle Scholar
  84. 84.
    Schwartz S, et al. High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell. 2013;155(6):1409–21.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Liu N, et al. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015;518(7540):560–4.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Wang X, He C. Reading RNA methylation codes through methyl-specific binding proteins. RNA Biol. 2014;11(6):669–72.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Wang X, et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161(6):1388–99.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Xiao W, et al. Nuclear m(6)A reader YTHDC1 regulates mRNA splicing. Mol Cell. 2016;61(4):507–19.PubMedCrossRefGoogle Scholar
  89. 89.
    Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292(5819):154–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981;78(12):7634–8.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Thomson JA, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282(5391):1145–7.PubMedCrossRefGoogle Scholar
  92. 92.
    Batista PJ, et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell. 2014;15(6):707–19.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Cui Q, et al. m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep. 2017;18(11):2622–34.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Horiuchi K, et al. Wilms’ tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci U S A. 2006;103(46):17278–83.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Cardelli M, et al. A polymorphism of the YTHDF2 gene (1p35) located in an Alu-rich genomic domain is associated with human longevity. J Gerontol A Biol Sci Med Sci. 2006;61(6):547–56.PubMedCrossRefGoogle Scholar
  96. 96.
    Daoud H, et al. Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. J Med Genet. 2016;53:200–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Frye M, Watt FM. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr Biol. 2006;16(10):971–81.PubMedCrossRefGoogle Scholar
  98. 98.
    Blanco S, et al. The RNA-methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genet. 2011;7(12):e1002403.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Hussain S, et al. The mouse Cytosine-5 RNA Methyltransferase NSun2 is a component of the Chromatoid body and required for testis differentiation. Mol Cell Biol. 2013;33(8):1561–70.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Khan MA, et al. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am J Hum Genet. 2012;90(5):856–63.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Martinez FJ, et al. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet. 2012;49(6):380–5.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Abbasi-Moheb L, et al. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am J Hum Genet. 2012;90(5):847–55.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Komara M, et al. A novel single-nucleotide deletion (c.1020delA) in NSUN2 causes intellectual disability in an emirati child. J Mol Neurosci. 2015;57:393.PubMedCrossRefGoogle Scholar
  104. 104.
    Ghadami S, et al. Frequencies of six (five novel) STR markers linked to TUSC3 (MRT7) or NSUN2 (MRT5) genes used for homozygosity mapping of recessive intellectual disability. Clin Lab. 2015;61(8):925–32.PubMedGoogle Scholar
  105. 105.
    Schepeler T, Page ME, Jensen KB. Heterogeneity and plasticity of epidermal stem cells. Development. 2014;141(13):2559–67.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Thompson DM, et al. tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA. 2008;14(10):2095–103.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Wek RC, Jiang HY, Anthony TG. Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans. 2006;34(Pt 1):7–11.PubMedCrossRefGoogle Scholar
  108. 108.
    Signer RA, et al. Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature. 2014;509(7498):49–54.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Llorens-Bobadilla E, et al. Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell. 2015;17(3):329–40.PubMedCrossRefGoogle Scholar
  110. 110.
    Frye M, et al. Genomic gain of 5p15 leads to over-expression of Misu (NSUN2) in breast cancer. Cancer Lett. 2010;289:71–80.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.University of Cambridge, Department of GeneticsCambridgeUK
  2. 2.Department of Biomedical EngineeringKhalifa University of Science and TechnologyAbu DhabiUnited Arab Emirates

Personalised recommendations