1932

Abstract

In recent years, m6A has emerged as an abundant and dynamically regulated modification throughout the transcriptome. Recent technological advances have enabled the transcriptome-wide identification of m6A residues, which in turn has provided important insights into the biology and regulation of this pervasive regulatory mark. Also central to our current understanding of m6A are the discovery and characterization of m6A readers, writers, and erasers. Over the last few years, studies into the function of these proteins have led to important discoveries about the regulation and function of m6A. However, during this time our understanding of these proteins has also evolved considerably, sometimes leading to the reversal of early concepts regarding the reading, writing and erasing of m6A. In this review, we summarize recent advances in m6A research, and we highlight how these new findings have reshaped our understanding of how m6A is regulated in the transcriptome.

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2017-10-06
2024-12-08
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Literature Cited

  1. Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR. 2012. RNA methylation by the MIS complex regulates a cell fate decision in yeast. PLOS Genet 8:e1002732 [Google Scholar]
  2. Aguzzi A, Altmeyer M. 2016. Phase separation: linking cellular compartmentalization to disease. Trends Cell Biol 26:547–58 [Google Scholar]
  3. Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. 2015a. HNRNPA2B1 is a mediator of m6A-dependent nuclear RNA processing events. Cell 162:1299–308 [Google Scholar]
  4. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. 2015b. N6-Methyladenosine marks primary microRNAs for processing. Nature 519:482–85 [Google Scholar]
  5. Banko JL, Hou L, Poulin F, Sonenberg N, Klann E. 2006. Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression. J. Neurosci. 26:2167–73 [Google Scholar]
  6. Batista PJ, Molinie B, Wang J, Qu K, Zhang J. et al. 2014. m6A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 15:707–19 [Google Scholar]
  7. Bokar JA, Rath-Shambaugh ME, Ludwiczak R, Narayan P, Rottman F. 1994. Characterization and partial purification of mRNA N6-adenosine methyltransferase from HeLa cell nuclei. Internal mRNA methylation requires a multisubunit complex. J. Biol. Chem. 269:17697–704 [Google Scholar]
  8. Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM. 1997. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3:1233–47 [Google Scholar]
  9. Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV. 2014. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 515:143–46 [Google Scholar]
  10. Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W. et al. 2015. FTO obesity variant circuitry and adipocyte browning in humans. N. Engl. J. Med. 373:895–907 [Google Scholar]
  11. Cui Q, Shi H, Ye P, Li L, Qu Q. et al. 2017. m6A RNA methylation regulates the self-renewal and tumorigenesis of glioblastoma stem cells. Cell Rep 18:2622–34 [Google Scholar]
  12. de Breyne S, Yu Y, Pestova TV, Hellen CU. 2008. Factor requirements for translation initiation on the Simian picornavirus internal ribosomal entry site. RNA 14:367–80 [Google Scholar]
  13. Delatte B, Wang F, Ngoc LV, Collignon E, Bonvin E. et al. 2016. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 351:282–85 [Google Scholar]
  14. Desrosiers R, Friderici K, Rottman F. 1974. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. PNAS 71:3971–75 [Google Scholar]
  15. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L. et al. 2012. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485:201–6 [Google Scholar]
  16. Du H, Zhao Y, He J, Zhang Y, Xi H. et al. 2016. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat. Commun. 7:12626 [Google Scholar]
  17. Fawcett KA, Barroso I. 2010. The genetics of obesity: FTO leads the way. Trends Genet 26:266–74 [Google Scholar]
  18. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T. et al. 2009. Inactivation of the Fto gene protects from obesity. Nature 458:894–98 [Google Scholar]
  19. Fustin J-M, Doi M, Yamaguchi Y, Hida H, Nishimura S. et al. 2013. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 155:793–806 [Google Scholar]
  20. Geula S, Moshitch-Moshkovitz S, Dominissini D, Mansour AA, Kol N. et al. 2015. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347:1002–6 [Google Scholar]
  21. Gokhale NS, Horner SM. 2017. RNA modifications go viral. PLOS Pathog 13:e1006188 [Google Scholar]
  22. Gokhale NS, McIntyre AB, McFadden MJ, Roder AE, Kennedy EM. et al. 2016. N6-Methyladenosine in Flaviviridae viral RNA genomes regulates infection. Cell Host Microbe 20:654–65 [Google Scholar]
  23. Granadino B, Penalva LO, Sanchez L. 1996. The gene fl(2)d is needed for the sex-specific splicing of transformer pre-mRNA but not for double-sex pre-mRNA in Drosophila melanogaster. Mol. Gen. Genet. 253:26–31 [Google Scholar]
  24. Harper JE, Miceli SM, Roberts RJ, Manley JL. 1990. Sequence specificity of the human mRNA N6-adenosine methylase in vitro. Nucleic Acids Res 18:5735–41 [Google Scholar]
  25. Haussmann IU, Bodi Z, Sanchez-Moran E, Mongan NP, Archer N. et al. 2016. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 540:301–4 [Google Scholar]
  26. Hess ME, Hess S, Meyer KD, Verhagen LA, Koch L. et al. 2013. The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat. Neurosci. 16:1042–48 [Google Scholar]
  27. Hilfiker A, Amrein H, Dubendorfer A, Schneiter R, Nothiger R. 1995. The gene virilizer is required for female-specific splicing controlled by Sxl, the master gene for sexual development in Drosophila. Development 121:4017–26 [Google Scholar]
  28. Horiuchi K, Kawamura T, Iwanari H, Ohashi R, Naito M. et al. 2013. Identification of Wilms’ tumor 1–associating protein complex and its role in alternative splicing and the cell cycle. J. Biol. Chem. 288:33292–302 [Google Scholar]
  29. Jackson RJ, Hellen CU, Pestova TV. 2010. The mechanism of eukaryotic translation initiation and principles of its regulation. Nat. Rev. Mol. Cell Biol. 11:113–27 [Google Scholar]
  30. Jaffrey SR, Kharas MG. 2017. Emerging links between m6A and misregulated mRNA methylation in cancer. Genome Med 9:2 [Google Scholar]
  31. Jain S, Wheeler JR, Walters RW, Agrawal A, Barsic A, Parker R. 2016. ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164:487–98 [Google Scholar]
  32. Jia G, Fu Y, Zhao X, Dai Q, Zheng G. et al. 2011. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7:885–87 [Google Scholar]
  33. Jia G, Yang CG, Yang S, Jian X, Yi C. et al. 2008. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett 582:3313–19 [Google Scholar]
  34. Kan L, Grozhik AV, Vedanayagam J, Patil DP, Pang N. et al. 2017. The m6A pathway facilitates sex determination in Drosophila. Nat. Commun. 8:15737 [Google Scholar]
  35. Kato M, Han TW, Xie S, Shi K, Du X. et al. 2012. Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels. Cell 149:753–67 [Google Scholar]
  36. Ke S, Alemu EA, Mertens C, Gantman EC, Fak JJ. et al. 2015. A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev 29:2037–53 [Google Scholar]
  37. Keith JM, Ensinger MJ, Mose B. 1978. HeLa cell RNA (2′-O-methyladenosine-N6-)-methyltransferase specific for the capped 5′-end of messenger RNA. J. Biol. Chem 253:5033–39 [Google Scholar]
  38. Kennedy EM, Bogerd HP, Kornepati AV, Kang D, Ghoshal D. et al. 2016. Posttranscriptional m6A editing of HIV-1 mRNAs enhances viral gene expression. Cell Host Microbe 19:675–85 [Google Scholar]
  39. Kierzek E, Kierzek R. 2003. The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines. Nucleic Acids Res 31:4472–80 [Google Scholar]
  40. Knuckles P, Carl SH, Musheev M, Niehrs C, Wenger A, Buhler M. 2017. RNA fate determination through cotranscriptional adenosine methylation and microprocessor binding. Nat. Struct. Mol. Biol. 24:561–69 [Google Scholar]
  41. Konig J, Zarnack K, Rot G, Curk T, Kayikci M. et al. 2010. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol. 17:909–15 [Google Scholar]
  42. Lee AS, Kranzusch PJ, Cate JH. 2015. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature 522:111–14 [Google Scholar]
  43. Lee JT. 2009. Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev 23:1831–42 [Google Scholar]
  44. Lence T, Akhtar J, Bayer M, Schmid K, Spindler L. et al. 2016. m6A modulates neuronal functions and sex determination in Drosophila. Nature 540:242–47 [Google Scholar]
  45. Li Z, Weng H, Su R, Weng X, Zuo Z. et al. 2017. FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell 31:127–41 [Google Scholar]
  46. Lichinchi G, Zhao BS, Wu Y, Lu Z, Qin Y. et al. 2016. Dynamics of human and viral RNA methylation during Zika virus infection. Cell Host Microbe 20:666–73 [Google Scholar]
  47. Linder B, Grozhik AV, Olarerin-George AO, Meydan C, Mason CE, Jaffrey SR. 2015. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat. Methods 12:767–72 [Google Scholar]
  48. Liu J, Yue Y, Han D, Wang X, Fu Y. et al. 2014. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10:93–95 [Google Scholar]
  49. Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. 2015. N6-Methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 518:560–64 [Google Scholar]
  50. Liu N, Parisien M, Dai Q, Zheng G, He C, Pan T. 2013. Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA 19:1848–56 [Google Scholar]
  51. Lovejoy AF, Riordan DP, Brown PO. 2014. Transcriptome-wide mapping of pseudouridines: Pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLOS ONE 9:e110799 [Google Scholar]
  52. Luo S, Tong L. 2014. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. PNAS 111:13834–39 [Google Scholar]
  53. Martinez FJ, Pratt GA, van Nostrand EL, Batra R, Huelga SC. et al. 2016. Protein-RNA networks regulated by normal and ALS-associated mutant HNRNPA2B1 in the nervous system. Neuron 92:780–95 [Google Scholar]
  54. Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV. et al. 2017. Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 541:371–75 [Google Scholar]
  55. McGuinness D, McGuinness D. 2014. m6A RNA methylation: the implications for health and disease. J. Cancer Sci. Clin. Oncol. 1:1–7 [Google Scholar]
  56. Meyer KD, Jaffrey SR. 2014. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat. Rev. Mol. Cell Biol. 15:313–26 [Google Scholar]
  57. Meyer KD, Patil DP, Zhou J, Zinoviev A, Skabkin MA. et al. 2015. 5′ UTR m6A promotes cap-independent translation. Cell 163:999–1010 [Google Scholar]
  58. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. 2012. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149:1635–46 [Google Scholar]
  59. Morohashi K, Sahara H, Watashi K, Iwabata K, Sunoki T. et al. 2011. Cyclosporin A associated helicase-like protein facilitates the association of hepatitis C virus RNA polymerase with its cellular cyclophilin B. PLOS ONE 6:e18285 [Google Scholar]
  60. Narayan P, Rottman FM. 1988. An in vitro system for accurate methylation of internal adenosine residues in messenger RNA. Science 242:1159–62 [Google Scholar]
  61. Ortega A, Niksic M, Bachi A, Wilm M, Sanchez L. et al. 2003. Biochemical function of female-lethal (2)D/Wilms' tumor suppressor-1-associated proteins in alternative pre-mRNA splicing. J. Biol. Chem. 278:3040–47 [Google Scholar]
  62. Patil DP, Chen CK, Pickering BF, Chow A, Jackson C. et al. 2016. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537:369–73 [Google Scholar]
  63. Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y. et al. 2017. The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell 169:824–35.e14 [Google Scholar]
  64. Perry RP, Kelley DE. 1974. Existence of methylated messenger RNA in mouse L cells. Cell 1:37–42 [Google Scholar]
  65. Ping XL, Sun BF, Wang L, Xiao W, Yang X. et al. 2014. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 24:177–89 [Google Scholar]
  66. Richter JD, Sonenberg N. 2005. Regulation of cap-dependent translation by eIF4E inhibitory proteins. Nature 433:477–80 [Google Scholar]
  67. Roost C, Lynch SR, Batista PJ, Qu K, Chang HY, Kool ET. 2015. Structure and thermodynamics of N6-methyladenosine in RNA: a spring-loaded base modification. J. Am. Chem. Soc. 137:2107–15 [Google Scholar]
  68. Schapira M. 2015. Structural chemistry of human RNA methyltransferases. ACS Chem. Biol. 11:575–82 [Google Scholar]
  69. Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH. et al. 2014a. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:148–62 [Google Scholar]
  70. Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K. et al. 2014b. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Rep 8:284–96 [Google Scholar]
  71. Shimba S, Bokar JA, Rottman F, Reddy R. 1995. Accurate and efficient N6-adenosine methylation in spliceosomal U6 small nuclear RNA by HeLa cell extract in vitro. Nucleic Acids Res 23:2421–26 [Google Scholar]
  72. Sledz P, Jinek M. 2016. Structural insights into the molecular mechanism of the m6A writer complex. eLife 5:e18434 [Google Scholar]
  73. Slobodin B, Han R, Calderone V, Vrielink JA, Loayza-Puch F. et al. 2017. Transcription impacts the efficiency of mRNA translation via co-transcriptional N6-adenosine methylation. Cell 169:326–37.e12 [Google Scholar]
  74. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ. et al. 2014. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507:371–75 [Google Scholar]
  75. Sommer S, Lavi U, Darnell JE Jr.. 1978. The absolute frequency of labeled N6-methyladenosine in HeLa cell messenger RNA decreases with label time. J. Mol. Biol. 124:487–99 [Google Scholar]
  76. Spitale RC, Flynn RA, Zhang QC, Crisalli P, Lee B. et al. 2015. Structural imprints in vivo decode RNA regulatory mechanisms. Nature 519:486–90 [Google Scholar]
  77. Stoilov P, Rafalska I, Stamm S. 2002. YTH: a new domain in nuclear proteins. Trends Biochem. Sci. 27:495–97 [Google Scholar]
  78. Stratigopoulos G, Burnett LC, Rausch R, Gill R, Penn DB. et al. 2016. Hypomorphism of Fto and Rpgrip1l causes obesity in mice. J. Clin. Investig 126:1897–910 [Google Scholar]
  79. Sun C, Querol-Audi J, Mortimer SA, Arias-Palomo E, Doudna JA. et al. 2013. Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation. Nucleic Acids Res 41:7512–21 [Google Scholar]
  80. Tanabe A, Tanikawa K, Tsunetomi M, Takai K, Ikeda H. et al. 2016. RNA helicase YTHDC2 promotes cancer metastasis via the enhancement of the efficiency by which HIF-1α mRNA is translated. Cancer Lett 376:34–42 [Google Scholar]
  81. Theler D, Dominguez C, Blatter M, Boudet J, Allain FH. 2014. Solution structure of the YTH domain in complex with N6-methyladenosine RNA: a reader of methylated RNA. Nucleic Acids Res 42:13911–19 [Google Scholar]
  82. Tirumuru N, Zhao BS, Lu W, Lu Z, He C, Wu L. 2016. N6-Methyladenosine of HIV-1 RNA regulates viral infection and HIV-1 Gag protein expression. eLife 5:e15528 [Google Scholar]
  83. Wang C, Zhu Y, Bao H, Jiang Y, Xu C. et al. 2016. A novel RNA-binding mode of the YTH domain reveals the mechanism for recognition of determinant of selective removal by Mmi1. Nucleic Acids Res 44:969–82 [Google Scholar]
  84. Wang P, Doxtader KA, Nam Y. 2016. Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases. Mol. Cell 63:306–17 [Google Scholar]
  85. Wang X, Feng J, Xue Y, Guan Z, Zhang D. et al. 2016. Structural basis of N6-adenosine methylation by the METTL3-METTL14 complex. Nature 534:575–78 [Google Scholar]
  86. Wang X, Lu Z, Gomez A, Hon GC, Yue Y. et al. 2014. N6-Methyladenosine-dependent regulation of messenger RNA stability. Nature 505:117–20 [Google Scholar]
  87. Wang X, Zhao BS, Roundtree IA, Lu Z, Han D. et al. 2015. N6-Methyladenosine modulates messenger RNA translation efficiency. Cell 161:1388–99 [Google Scholar]
  88. Wang Y, Li Y, Toth JI, Petroski MD, Zhang Z, Zhao JC. 2014. N6-Methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 16:191–98 [Google Scholar]
  89. Wei C, Gershowitz A, Moss B. 1975. N6, O2′-dimethyladenosine a novel methylated ribonucleoside next to the 5′ terminal of animal cell and virus mRNAs. Nature 257:251–53 [Google Scholar]
  90. Wei CM, Gershowitz A, Moss B. 1976. 5′-Terminal and internal methylated nucleotide sequences in HeLa cell mRNA. Biochemistry 15:397–401 [Google Scholar]
  91. Wei CM, Moss B. 1977. Nucleotide sequences at the N6-methyladenosine sites of HeLa cell messenger ribonucleic acid. Biochemistry 16:1672–76 [Google Scholar]
  92. Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ. et al. 2016. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61:507–19 [Google Scholar]
  93. Xu C, Liu K, Ahmed H, Loppnau P, Schapira M, Min J. 2015. Structural basis for the discriminative recognition of N6-methyladenosine RNA by the human YT521-B homology domain family of proteins. J. Biol. Chem. 290:24902–13 [Google Scholar]
  94. Xu C, Wang X, Liu K, Roundtree IA, Tempel W. et al. 2014. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat. Chem. Biol. 10:927–29 [Google Scholar]
  95. Zhang C, Samanta D, Lu H, Bullen JW, Zhang H. et al. 2016a. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. PNAS 113:E2047–56 [Google Scholar]
  96. Zhang C, Zhi WI, Lu H, Samanta D, Chen I. et al. 2016b. Hypoxia-inducible factors regulate pluripotency factor expression by ZNF217- and ALKBH5-mediated modulation of RNA methylation in breast cancer cells. Oncotarget 7:64527–42 [Google Scholar]
  97. Zhang S, Zhao BS, Zhou A, Lin K, Zheng S. et al. 2017. m6A demethylase ALKBH5 maintains tumorigenicity of glioblastoma stem-like cells by sustaining FOXM1 expression and cell proliferation program. Cancer Cell 31:591–606.e6 [Google Scholar]
  98. Zhang Z, Theler D, Kaminska KH, Hiller M, de la Grange P. et al. 2010. The YTH domain is a novel RNA binding domain. J. Biol. Chem. 285:14701–10 [Google Scholar]
  99. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM. et al. 2013. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49:18–29 [Google Scholar]
  100. Zhong S, Li H, Bodi Z, Button J, Vespa L. et al. 2008. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 20:1278–88 [Google Scholar]
  101. Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB. 2015. Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature 526:591–94 [Google Scholar]
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