1932

Abstract

Chemical modifications on mRNA represent a critical layer of gene expression regulation. Research in this area has continued to accelerate over the last decade, as more modifications are being characterized with increasing depth and breadth. mRNA modifications have been demonstrated to influence nearly every step from the early phases of transcript synthesis in the nucleus through to their decay in the cytoplasm, but in many cases, the molecular mechanisms involved in these processes remain mysterious. Here, we highlight recent work that has elucidated the roles of mRNA modifications throughout the mRNA life cycle, describe gaps in our understanding and remaining open questions, and offer some forward-looking perspective on future directions in the field.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-052521-035949
2023-06-20
2024-06-21
Loading full text...

Full text loading...

/deliver/fulltext/biochem/92/1/annurev-biochem-052521-035949.html?itemId=/content/journals/10.1146/annurev-biochem-052521-035949&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S et al. 2022. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res 50:D1D231–35
    [Google Scholar]
  2. 2.
    Gilbert WV, Bell TA, Schaening C. 2016. Messenger RNA modifications: form, distribution, and function. Science 352:62921408–12
    [Google Scholar]
  3. 3.
    Harcourt EM, Kietrys AM, Kool ET. 2017. Chemical and structural effects of base modifications in messenger RNA. Nature 541:339–46
    [Google Scholar]
  4. 4.
    Owens MC, Zhang C, Liu KF. 2021. Recent technical advances in the study of nucleic acid modifications. Mol. Cell 81:204116–36
    [Google Scholar]
  5. 5.
    Nachtergaele S, He C. 2018. Chemical modifications in the life of an mRNA transcript. Annu. Rev. Genet. 52:349–72
    [Google Scholar]
  6. 6.
    He PC, He C. 2021. m6A RNA methylation: from mechanisms to therapeutic potential. EMBO J 40:3e105977
    [Google Scholar]
  7. 7.
    Murakami S, Jaffrey SR. 2022. Hidden codes in mRNA: control of gene expression by m6A. Mol. Cell 82:122236–51
    [Google Scholar]
  8. 8.
    Ke S, Pandya-Jones A, Saito Y, Fak JJ, Vågbø CB et al. 2017. m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover. Genes Dev 31:10990–1006
    [Google Scholar]
  9. 9.
    Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM et al. 2012. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 150:2279–90
    [Google Scholar]
  10. 10.
    Louloupi A, Ntini E, Conrad T, Ørom UAV 2018. Transient N-6-methyladenosine transcriptome sequencing reveals a regulatory role of m6A in splicing efficiency. Cell Rep 23:123429–37
    [Google Scholar]
  11. 11.
    Huang H, Weng H, Zhou K, Wu T, Zhao BS et al. 2019. Histone H3 trimethylation at lysine 36 guides m6A RNA modification co-transcriptionally. Nature 567:7748414–19
    [Google Scholar]
  12. 12.
    Jonkers I, Lis JT. 2015. Getting up to speed with transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell. Biol. 16:3167–77
    [Google Scholar]
  13. 13.
    Martinez NM, Gilbert WV. 2018. Pre-mRNA modifications and their role in nuclear processing. Quant. Biol. 6:3210–27
    [Google Scholar]
  14. 14.
    Martinez NM, Su A, Burns MC, Nussbacher JK, Schaening C et al. 2022. Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing. Mol. Cell 82:3645–59.e9
    [Google Scholar]
  15. 15.
    Ji X, Dadon DB, Abraham BJ, Lee TI, Jaenisch R et al. 2015. Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions. PNAS 112:123841–46
    [Google Scholar]
  16. 16.
    Amort T, Rieder D, Wille A, Khokhlova-Cubberley D, Riml C et al. 2017. Distinct 5-methylcytosine profiles in poly(A) RNA from mouse embryonic stem cells and brain. Genome Biol 18:11
    [Google Scholar]
  17. 17.
    Delatte B, Wang F, Ngoc LV, Collignon E, Bonvin E et al. 2016. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 351:6270282–85
    [Google Scholar]
  18. 18.
    Lan J, Rajan N, Bizet M, Penning A, Singh NK et al. 2020. Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation. Nat. Commun. 11:14956
    [Google Scholar]
  19. 19.
    Zhou H, Rauch S, Dai Q, Cui X, Zhang Z et al. 2019. Evolution of a reverse transcriptase to map N1-methyladenosine in human messenger RNA. Nat. Methods 16:121281–88
    [Google Scholar]
  20. 20.
    Draycott AS, Schaening-Burgos C, Rojas-Duran MF, Wilson L, Schärfen L et al. 2022. Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA. PLOS Biol 20:5e3001622
    [Google Scholar]
  21. 21.
    Aguilo F, Li S, Balasubramaniyan N, Sancho A, Benko S et al. 2016. Deposition of 5-methylcytosine on enhancer RNAs enables the coactivator function of PGC-1α. Cell Rep 14:3479–92
    [Google Scholar]
  22. 22.
    Huttlin EL, Bruckner RJ, Navarrete-Perea J, Cannon JR, Baltier K et al. 2021. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 184:113022–40.e28
    [Google Scholar]
  23. 23.
    Arango D, Sturgill D, Alhusaini N, Dillman AA, Sweet TJ et al. 2018. Acetylation of cytidine in mRNA promotes translation efficiency. Cell 175:71872–86.e24
    [Google Scholar]
  24. 24.
    Sleiman S, Dragon F. 2019. Recent advances on the structure and function of RNA acetyltransferase Kre33/NAT10. Cells 8:91035
    [Google Scholar]
  25. 25.
    Ayadi L, Galvanin A, Pichot F, Marchand V, Motorin Y. 2019. RNA ribose methylation (2′-O-methylation): occurrence, biosynthesis and biological functions. Biochim. Biophys. Acta Gene Regul. Mech. 1862:3253–69
    [Google Scholar]
  26. 26.
    Dai Q, Moshitch-Moshkovitz S, Han D, Kol N, Amariglio N et al. 2017. Nm-seq maps 2′-O-methylation sites in human mRNA with base precision. Nat. Methods 14:7695–98
    [Google Scholar]
  27. 27.
    Elliott BA, Ho HT, Ranganathan SV, Vangaveti S, Ilkayeva O et al. 2019. Modification of messenger RNA by 2′-O-methylation regulates gene expression in vivo. Nat. Commun. 10:13401
    [Google Scholar]
  28. 28.
    Xu W, He C, Kaye EG, Li J, Mu M et al. 2022. Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis. Mol. Cell 82:61156–68.e7
    [Google Scholar]
  29. 29.
    Akhtar J, Renaud Y, Albrecht S, Ghavi-Helm Y, Roignant JY et al. 2021. m6A RNA methylation regulates promoter-proximal pausing of RNA polymerase II. Mol. Cell 81:163356–67.e6
    [Google Scholar]
  30. 30.
    Barbieri I, Tzelepis K, Pandolfini L, Shi J, Millán-Zambrano G et al. 2017. Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control. Nature 552:7683126–31
    [Google Scholar]
  31. 31.
    Dai X, Wang T, Gonzalez G, Wang Y. 2018. Identification of YTH domain-containing proteins as the readers for N1-methyladenosine in RNA. Anal. Chem. 90:116380–84
    [Google Scholar]
  32. 32.
    Seo KW, Kleiner RE. 2020. YTHDF2 recognition of N1-methyladenosine (m1A)-modified RNA is associated with transcript destabilization. ACS Chem. Biol. 15:1132–39
    [Google Scholar]
  33. 33.
    Lee JH, Wang R, Xiong F, Krakowiak J, Liao Z et al. 2021. Enhancer RNA m6A methylation facilitates transcriptional condensate formation and gene activation. Mol. Cell 81:163368–85.e9
    [Google Scholar]
  34. 34.
    Hnisz D, Shrinivas K, Young RA, Chakraborty AK, Sharp PA. 2017. A phase separation model for transcriptional control. Cell 169:113–23
    [Google Scholar]
  35. 35.
    Liu J, Dou X, Chen C, Chen C, Liu C et al. 2020. N6-Methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367:6477580–86
    [Google Scholar]
  36. 36.
    Pillutla RC, Yue Z, Maldonado E, Shatkin AJ. 1998. Recombinant human mRNA cap methyltransferase binds capping enzyme/RNA polymerase IIo complexes. J. Biol. Chem. 273:3421443–46
    [Google Scholar]
  37. 37.
    Tsukamoto T, Shibagaki Y, Niikura Y, Mizumoto K. 1998. Cloning and characterization of three human cDNAs encoding mRNA (guanine-7-)-methyltransferase, an mRNA cap methylase. Biochem. Biophys. Res. Commun. 251:127–34
    [Google Scholar]
  38. 38.
    Langberg SR, Moss B. 1981. Post-transcriptional modifications of mRNA. Purification and characterization of cap I and cap II RNA (nucleoside-2′-)-methyltransferases from HeLa cells. J. Biol. Chem. 256:1910054–60
    [Google Scholar]
  39. 39.
    Hinnebusch AG, Ivanov IP, Sonenberg N. 2016. Translational control by 5′-untranslated regions of eukaryotic mRNAs. Science 352:62921413–16
    [Google Scholar]
  40. 40.
    Jiao X, Doamekpor SK, Bird JG, Nickels BE, Tong L et al. 2017. 5′ end nicotinamide adenine dinucleotide cap in human cells promotes RNA decay through DXO-mediated deNADding. Cell 168:61015–27.e10
    [Google Scholar]
  41. 41.
    Walters RW, Matheny T, Mizoue LS, Rao BS, Muhlrad D, Parker R. 2017. Identification of NAD+ capped mRNAs in Saccharomyces cerevisiae. PNAS 114:3480–85
    [Google Scholar]
  42. 42.
    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]
  43. 43.
    Chen YG, Kowtoniuk WE, Agarwal I, Shen Y, Liu DR. 2009. LC/MS analysis of cellular RNA reveals NAD-linked RNA. Nat. Chem. Biol. 5:12879–81
    [Google Scholar]
  44. 44.
    Cahová H, Winz M-L, Höfer K, Nübel G, Jäschke A. 2015. NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs. Nature 519:7543374–77
    [Google Scholar]
  45. 45.
    Lim J, Ha M, Chang H, Kwon SC, Simanshu DK et al. 2014. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell 159:61365–76
    [Google Scholar]
  46. 46.
    Akichika S, Hirano S, Shichino Y, Suzuki T, Nishimasu H et al. 2019. Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase. Science 363:6423eaav0080
    [Google Scholar]
  47. 47.
    Boulias K, Toczydlowska-Socha D, Hawley BR, Liberman N, Takashima K et al. 2019. Identification of the m6Am methyltransferase PCIF1 reveals the location and functions of m6Am in the transcriptome. Mol. Cell 75:3631–43.e8
    [Google Scholar]
  48. 48.
    Sendinc E, Valle-Garcia D, Dhall A, Chen H, Henriques T et al. 2019. PCIF1 catalyzes m6Am mRNA methylation to regulate gene expression. Mol. Cell 75:3620–30.e9
    [Google Scholar]
  49. 49.
    Pandey RR, Delfino E, Homolka D, Roithova A, Chen KM et al. 2020. The mammalian cap-specific m6Am RNA methyltransferase PCIF1 regulates transcript levels in mouse tissues. Cell Rep 32:7108038
    [Google Scholar]
  50. 50.
    Sharova LV, Sharov AA, Nedorezov T, Piao Y, Shaik N, Ko MSH. 2009. Database for mRNA half-life of 19 977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells. DNA Res 16:145–58
    [Google Scholar]
  51. 51.
    Wang J, Chew BLA, Lai Y, Dong H, Xu L et al. 2019. Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA. Nucleic Acids Res 47:20e130
    [Google Scholar]
  52. 52.
    Pandolfini L, Barbieri I, Bannister AJ, Hendrick A, Andrews B et al. 2019. METTL1 promotes let-7 microRNA processing via m7G methylation. Mol. Cell 74:61278–90.e9
    [Google Scholar]
  53. 53.
    Zhang LS, Liu C, Ma H, Dai Q, Sun HL et al. 2019. Transcriptome-wide mapping of internal N7-methylguanosine methylome in mammalian mRNA. Mol. Cell 74:61304–16.e8
    [Google Scholar]
  54. 54.
    Enroth C, Poulsen LD, Iversen S, Kirpekar F, Albrechtsen A, Vinther J. 2019. Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing. Nucleic Acids Res 47:20e126
    [Google Scholar]
  55. 55.
    Fu XD, Ares M. 2014. Context-dependent control of alternative splicing by RNA-binding proteins. Nat. Rev. Genet. 15:10689–701
    [Google Scholar]
  56. 56.
    Nilsen TW, Graveley BR. 2010. Expansion of the eukaryotic proteome by alternative splicing. Nature 463:7280457–63
    [Google Scholar]
  57. 57.
    Wright CJ, Smith CWJ, Jiggins CD. 2022. Alternative splicing as a source of phenotypic diversity. Nat. Rev. Genet. 23:697–710
    [Google Scholar]
  58. 58.
    Zhao X, Yang Y, Sun B-F, Shi Y, Yang X et al. 2014. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res 24:121403–19
    [Google Scholar]
  59. 59.
    Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. 2015. N6-Methyladenosine-dependent RNA structural switches regulate RNA–protein interactions. Nature 518:7540560–64
    [Google Scholar]
  60. 60.
    Phizicky EM, Hopper AK. 2010. tRNA biology charges to the front. Genes Dev 24:171832–60
    [Google Scholar]
  61. 61.
    Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E et al. 2021. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature 593:7860597–601
    [Google Scholar]
  62. 62.
    Kanemaki MT. 2022. Ligand-induced degrons for studying nuclear functions. Curr. Opin. Cell Biol. 74:29–36
    [Google Scholar]
  63. 63.
    Wei G, Almeida M, Pintacuda G, Coker H, Bowness JS et al. 2021. Acute depletion of METTL3 implicates N6-methyladenosine in alternative intron/exon inclusion in the nascent transcriptome. Genome Res 31:81395–408
    [Google Scholar]
  64. 64.
    Borchardt EK, Martinez NM, Gilbert W V. 2020. Regulation and function of RNA pseudouridylation in human cells. Annu. Rev. Genet. 54:309–36
    [Google Scholar]
  65. 65.
    Xiao W, Adhikari S, Dahal U, Chen Y-S, Hao Y-J et al. 2016. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61:4507–19
    [Google Scholar]
  66. 66.
    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 540:7632301–4
    [Google Scholar]
  67. 67.
    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]
  68. 68.
    Van Nostrand EL, Freese P, Pratt GA, Wang X, Wei X et al. 2020. A large-scale binding and functional map of human RNA-binding proteins. Nature 583:7818711–19
    [Google Scholar]
  69. 69.
    Mitschka S, Mayr C. 2022. Context-specific regulation and function of mRNA alternative polyadenylation. Nat. Rev. Mol. Cell. Biol. 23:779–96
    [Google Scholar]
  70. 70.
    Lesbirel S, Viphakone N, Parker M, Parker J, Heath C et al. 2018. The m6A-methylase complex recruits TREX and regulates mRNA export. Sci. Rep. 8:113827
    [Google Scholar]
  71. 71.
    Yang X, Yang Y, Sun B-F, Chen Y-S, Xu J-W et al. 2017. 5-Methylcytosine promotes mRNA export—NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Res 27:5606–25
    [Google Scholar]
  72. 72.
    Blanco S, Dietmann S, Flores J V, Hussain S, Kutter C et al. 2014. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J 33:182020–39
    [Google Scholar]
  73. 73.
    Shi M, Zhang H, Wu X, He Z, Wang L et al. 2017. ALYREF mainly binds to the 5′ and the 3′ regions of the mRNA in vivo. Nucleic Acids Res 45:169640–53
    [Google Scholar]
  74. 74.
    Roundtree IA, Luo GZ, Zhang Z, Wang X, Zhou T et al. 2017. YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs. eLife 6:e31311
    [Google Scholar]
  75. 75.
    Edens BM, Vissers C, Su J, Arumugam S, Xu Z et al. 2019. FMRP modulates neural differentiation through m6A-dependent mRNA nuclear export. Cell Rep 28:4845–54.e5
    [Google Scholar]
  76. 76.
    Courtney DG, Chalem A, Bogerd HP, Law BA, Kennedy EM et al. 2019. Extensive epitranscriptomic methylation of A and C residues on murine leukemia virus transcripts enhances viral gene expression. mBio 10:3e01209-19
    [Google Scholar]
  77. 77.
    Mougel M, Akkawi C, Chamontin C, Feuillard J, Pessel-Vivares L et al. 2020. NXF1 and CRM1 nuclear export pathways orchestrate nuclear export, translation and packaging of murine leukaemia retrovirus unspliced RNA. RNA Biol 17:4528–38
    [Google Scholar]
  78. 78.
    Rauch S, He E, Srienc M, Zhou H, Zhang Z, Dickinson BC. 2019. Programmable RNA-guided RNA effector proteins built from human parts. Cell 178:1122–34.e12
    [Google Scholar]
  79. 79.
    Franco MK, Koutmou KS. 2022. Chemical modifications to mRNA nucleobases impact translation elongation and termination. Biophys. Chem. 285:106780
    [Google Scholar]
  80. 80.
    Arango D, Sturgill D, Yang R, Kanai T, Bauer P et al. 2022. Direct epitranscriptomic regulation of mammalian translation initiation through N4-acetylcytidine. Mol. Cell 82:152797–814.e11
    [Google Scholar]
  81. 81.
    Hinnebusch AG. 2017. Structural insights into the mechanism of scanning and start codon recognition in eukaryotic translation initiation. Trends Biochem. Sci. 42:8589–611
    [Google Scholar]
  82. 82.
    Jian H, Zhang C, Qi ZY, Li X, Lou Y et al. 2021. Alteration of mRNA 5-methylcytosine modification in neurons after OGD/R and potential roles in cell stress response and apoptosis. Front. Genet. 12:633681
    [Google Scholar]
  83. 83.
    Guo G, Wang H, Shi X, Ye L, Yan K et al. 2020. Disease activity-associated alteration of mRNA m5 C methylation in CD4+ T cells of systemic lupus erythematosus. Front. Cell Dev. Biol. 8:430
    [Google Scholar]
  84. 84.
    Schumann U, Zhang HN, Sibbritt T, Pan A, Horvath A et al. 2020. Multiple links between 5-methylcytosine content of mRNA and translation. BMC Biol 18:140
    [Google Scholar]
  85. 85.
    Yang L, Perrera V, Saplaoura E, Apelt F, Bahin M et al. 2019. m5C methylation guides systemic transport of messenger RNA over graft junctions in plants. Curr. Biol. 29:152465–76.e5
    [Google Scholar]
  86. 86.
    Jones JD, Monroe J, Koutmou KS. 2020. A molecular-level perspective on the frequency, distribution, and consequences of messenger RNA modifications. WIRES RNA 11:4e1586
    [Google Scholar]
  87. 87.
    Wang X, Liu A. 2022. The pivotal role of chemical modifications in mRNA therapeutics. Front. Cell Dev. Biol. 10:1264
    [Google Scholar]
  88. 88.
    Niederer RO, Rojas-Duran MF, Zinshteyn B, Gilbert WV. 2022. Direct analysis of ribosome targeting illuminates thousand-fold regulation of translation initiation. Cell Syst 13:3256–64.e3
    [Google Scholar]
  89. 89.
    Kierzek E, Malgowska M, Lisowiec J, Turner DH, Gdaniec Z, Kierzek R. 2014. The contribution of pseudouridine to stabilities and structure of RNAs. Nucleic Acids Res 42:53492–501
    [Google Scholar]
  90. 90.
    Dalluge JJ, Hashizume T, Sopchik AE, McCloskey JA, Davis DR. 1996. Conformational flexibility in RNA: the role of dihydrouridine. Nucleic Acids Res 24:61073–79
    [Google Scholar]
  91. 91.
    Dyubankova N, Sochacka E, Kraszewska K, Nawrot B, Herdewijn P, Lescrinier E. 2015. Contribution of dihydrouridine in folding of the D-arm in tRNA. Org. Biomol. Chem. 13:174960–66
    [Google Scholar]
  92. 92.
    Bartee D, Nance KD, Meier JL. 2022. Site-specific synthesis of N4-acetylcytidine in RNA reveals physiological duplex stabilization. J. Am. Chem. Soc. 144:83487–96
    [Google Scholar]
  93. 93.
    Helm M. 2006. Post-transcriptional nucleotide modification and alternative folding of RNA. Nucleic Acids Res 34:2721–33
    [Google Scholar]
  94. 94.
    Wang X, Lu Z, Gomez A, Hon GC, Yue Y et al. 2014. N6-Methyladenosine-dependent regulation of messenger RNA stability. Nature 505:7481117–20
    [Google Scholar]
  95. 95.
    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]
  96. 96.
    Hussain S, Aleksic J, Blanco S, Dietmann S, Frye M. 2013. Characterizing 5-methylcytosine in the mammalian epitranscriptome. Genome Biol 14:11215
    [Google Scholar]
  97. 97.
    Khoddami V, Cairns BR. 2013. Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat. Biotechnol. 31:5458–64
    [Google Scholar]
  98. 98.
    Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT et al. 2012. Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res 40:115023–33
    [Google Scholar]
  99. 99.
    Huang T, Chen W, Liu J, Gu N, Zhang R. 2019. Genome-wide identification of mRNA 5-methylcytosine in mammals. Nat. Struct. Mol. Biol. 26:5380–88
    [Google Scholar]
  100. 100.
    Yartseva V, Giraldez AJ. 2015. The maternal-to-zygotic transition during vertebrate development. Curr. Top. Dev. Biol. 113:191–232
    [Google Scholar]
  101. 101.
    Yang Y, Wang L, Han X, Yang W-L, Zhang M et al. 2019. RNA 5-methylcytosine facilitates the maternal-to-zygotic transition by preventing maternal mRNA decay. Mol. Cell 75:61188–202.e11
    [Google Scholar]
  102. 102.
    Evans MK, Matsui Y, Xu B, Willis C, Loome J et al. 2020. Ybx1 fine-tunes PRC2 activities to control embryonic brain development. Nat. Commun. 11:14060
    [Google Scholar]
  103. 103.
    Chen X, Li A, Sun BF, Yang Y, Han YN et al. 2019. 5-Methylcytosine promotes pathogenesis of bladder cancer through stabilizing mRNAs. Nat. Cell Biol. 21:8978–90
    [Google Scholar]
  104. 104.
    Zhao BS, Wang X, Beadell AV, Lu Z, Shi H et al. 2017. m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition. Nature 542:7642475–78
    [Google Scholar]
  105. 105.
    Su R, Dong L, Li C, Nachtergaele S, Wunderlich M et al. 2018. R-2HG exhibits anti-tumor activity by targeting FTO/m6A/MYC/CEBPA signaling. Cell 172:1–290–105.e23
    [Google Scholar]
  106. 106.
    Liu J, Eckert MA, Harada BT, Liu S-M, Lu Z et al. 2018. m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat. Cell Biol. 20:91074–83
    [Google Scholar]
  107. 107.
    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 515:7525143–46
    [Google Scholar]
  108. 108.
    Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH et al. 2014. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 159:1148–62
    [Google Scholar]
  109. 109.
    Lovejoy AF, Riordan DP, Brown PO. 2014. Transcriptome-wide mapping of pseudouridines: pseudouridine synthases modify specific mRNAs in S. cerevisiae. PLOS ONE 9:10e110799
    [Google Scholar]
  110. 110.
    Nakamoto MA, Lovejoy AF, Cygan AM, Boothroyd JC. 2017. mRNA pseudouridylation affects RNA metabolism in the parasite Toxoplasma gondii. RNA 23:121834–49
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-052521-035949
Loading
/content/journals/10.1146/annurev-biochem-052521-035949
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error