The epitranscriptome of noncoding RNAs in cancer

Cancer Discovery

Volumn 7, Issue 4, 2017, Pages 359-368

  Esteller, Manel ^a,b,c   Pandolfi, Pier Paolo ^d  

^a BELLVITGE BIOMEDICAL RESEARCH INSTITUTE IDIBELL   (Spain)

^b INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^c UNIVERSITY OF BARCELONA   (Spain)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA KETOGLUTARATE DEPENDENT DIOXYGENASE FTO; DNA METHYLTRANSFERASE; DYSKERIN; LONG UNTRANSLATED RNA; MESSENGER RNA; MICRORNA; PIWI INTERACTING RNA; RIBOSOME RNA; RNA METHYLTRANSFERASE; SMALL NUCLEAR RNA; SMALL NUCLEOLAR RNA; SMALL UNTRANSLATED RNA; TRANSCRIPTOME; TRANSFER RNA; UNTRANSLATED RNA;

ARTICLE; CELL TRANSFORMATION; CHEMICAL MODIFICATION; EPIGENETICS; GENE EXPRESSION; GENE MUTATION; HUMAN; MALIGNANT NEOPLASM; NONHUMAN; POLYADENYLATION; RNA SPLICING; RNA STABILITY; RNA STRUCTURE; TRANSCRIPTOMICS; GENETIC EPIGENESIS; GENETICS; NEOPLASM; PATHOLOGY;

CELL TRANSFORMATION, NEOPLASTIC; EPIGENESIS, GENETIC; HUMANS; NEOPLASMS; RNA, UNTRANSLATED; TRANSCRIPTOME;

EID: 85017110311     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-16-1292     Document Type: Article

References (104)

1. Gilbert WV, Bell TA, Schaening C. Messenger RNA modifications: Form, distribution, and function. Science 2016;352:1408–12.
2. Heyn H, Esteller M. An adenine code for DNA: A second life for N6-methyladenine. Cell 2015;161:710–3.
3. Squires JE, Patel HR, Nousch M, Sibbritt T, Humphreys DT, Parker BJ, et al. Widespread occurrence of 5-methylcytosine in human coding and non–coding RNA. Nucleic Acids Res 2012;40:5023–33.
4. Khoddami V, Cairns BR. Identification of direct targets and modified bases of RNA cytosine methyltransferases. Nat Biotechnol 2013; 31:458–64.
5. Hussain S, Aleksic J, Blanco S, Dietmann S, Frye M. Characterizing 5–methylcytosine in the mammalian epitranscriptome. Genome Biol 2013;14:215.
6. Delatte B, Wang F, Ngoc LV, Collignon E, Bonvin E, Deplus R, et al. RNA biochemistry. Transcriptome-wide distribution and function of RNA hydroxymethylcytosine. Science 2016;351:282–5.
7. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485:201–6.
8. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 2012;149:1635–46.
9. Dominissini D, Nachtergaele S, Moshitch-Moshkovitz S, Peer E, Kol N, Ben-Haim MS, et al. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature 2016;530:441–6.
10. Li X, Xiong X, Wang K, Wang L, Shu X, Ma S, et al. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. Nat Chem Biol 2016;12:311–6.
11. Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, León–Ricardo, et al. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 2014;159:148–62.
12. Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 2014;515:143–6.
13. Li X, Zhu P, Ma S, Song J, Bai J, Sun F, et al. Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome. Nat Chem Biol 2015;11:592–7.
14. Bazak L, Haviv A, Barak M, Jacob-Hirsch J, Deng P, Zhang R, et al. A–to–I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Res 2014;24:365–6.
15. Frye M, Blanco S. Post-transcriptional modifications in development and stem cells. Development 2016;143:3871–81.
16. Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 2017;18:31–42.
17. Ramanathan A, Robb GB, Chan SH. mRNA capping: Biological functions and applications. Nucleic Acids Res 2016;pii:gkw551.
18. Hussain S, Sajini AA, Blanco S, Dietmann S, Lombard P, Sugimoto Y, et al. NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs. Cell Rep 2013;4:255–61.
19. Tycowski KT, Aab A, Steitz JA. Guide RNAs with 5′ caps and novel box C/D snoRNA-like domains for modification of snRNAs in metazoa. Curr Biol 2004;14:1985–95.
20. Amort T, Soulière MF, Wille A, Jia XY, Fiegl H, Wörle H, et al. Long non–coding RNAs as targets for cytosine methylation. RNA Biol 2013;10:1003–8.
21. Fu L, Guerrero CR, Zhong N, Amato NJ, Liu Y, Liu S, et al. Tet– mediated formation of 5-hydroxymethylcytosine in RNA. J Am Chem Soc 2014;136:11582–5.
22. Lee M, Kim B, Kim VN. Emerging roles of RNA modification: m(6) A and U–tail. Cell 2014;158:980–7.
23. Alarcón CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature 2015a;519:482–5.
24. Alarcón CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF. HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell 2015b;162:1299–308.
25. Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 2013;73:1180–9.
26. Liu N, Parisien M, Dai Q, Zheng G, He C, Pan T. Probing N6-methyladenosine RNA modification status at single nucleotide resolution in mRNA and long noncoding RNA. RNA 2013;19:1848–56.
27. Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M, et al. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 2016;537:369–73.
28. Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K, Bushkin GG, et al. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5′ sites. Cell Rep 2014;8: 284–96.
29. Linder B, Grozhik AV, Olarerin-George AO, Meydan C, Mason CE, Jaffrey SR. Single-nucleotide-resolution mapping of m6A and m6Am throughout the transcriptome. Nat Methods 2015;12: 767–72.
30. Ge J, Yu YT. RNA pseudouridylation: New insights into an old modification. Trends Biochem Sci 2013;38:210–8.
31. Zaborske JM, DuMont VL, Wallace EW, Pan T, Aquadro CF, Drummond DA. A nutrient–driven tRNA modification alters translational fidelity and genome–wide protein coding across an animal genus. PLoS Biol 2014;12:e1002015.
32. Shafik A, Schumann U, Evers M, Sibbritt T, Preiss T. The emerging epitranscriptomics of long noncoding RNAs. Biochim Biophys Acta 2016;1859:59–70.
33. Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell 2008; 32:276–84.
34. Newman MA, Mani V, Hammond SM. Deep sequencing of micro-RNA precursors reveals extensive 3′ end modification. RNA 2011;17: 1795–803.
35. Heo I, Ha M, Lim J, Yoon MJ, Park JE, Kwon SC, et al. Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs. Cell 2012;151:521–32.
36. Zhang J, Manley JL. Misregulation of pre-mRNA alternative splicing in cancer. Cancer Discov 2013;3:1228–37.
37. Avesson L, Barry G. The emerging role of RNA and DNA editing in cancer. Biochim Biophys Acta 2014;1845:308–16.
38. Nik-Zainal S, Alexandrov LB, Wedge DC, Van Loo P, Greenman CD, Raine K, et al. Breast cancer working group of the international cancer genome consortium. Mutational processes molding the genomes of 21 breast cancers. Cell 2012;149:979–93.
39. Burns MB, Temiz NA, Harris RS. Evidence for APOBEC3B mutagen-esis in multiple human cancers. Nat Genet 2013;45:977–83.
40. Nik-Zainal S, Wedge DC, Alexandrov LB, Petljak M, Butler AP, Bolli N, et al. Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer. Nat Genet 2014;46:487–91.
41. Chen L, Li Y, Lin CH, Chan TH, Chow RK, Song Y, et al. Recoding RNA editing of AZIN1 predisposes to hepatocellular carcinoma. Nat Med 2013;19:209–16.
42. Anadón C, Guil S, Simó-Riudalbas L, Moutinho C, Setien F, Martínez-Cardús A, et al. Gene amplification–associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis. Oncogene 2016;35:4407–13.
43. Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature 1979;280:339–40.
44. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013;19:141–57.
45. Barrett SP, Wang PL, Salzman J. Circular RNA biogenesis can proceed through an exon-containing lariat precursor. Elife 2015; 4:e07540.
46. Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 2015;10:170–7.
47. Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, et al. Oncogenic role of fusion–circRNAs derived from cancer-associated chromosomal translocations. Cell 2016;165:289–302.
48. Grudzien-Nogalska E, Kiledjian M. New insights into decapping enzymes and selective mRNA decay. Wiley Interdiscip Rev RNA 2016;8.
49. Goll MG, Kirpekar F, Maggert KA, Yoder JA, Hsieh CL, Zhang X, et al. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 2006;311:395–8.
50. Schaefer M, Pollex T, Hanna K, Tuorto F, Meusburger M, Helm M, et al. RNA methylation by Dnmt2 protects transfer RNAs against stress–induced cleavage. Genes Dev 2010;24:1590–5.
51. Elhardt W, Shanmugam R, Jurkowski TP, Jeltsch A. Somatic cancer mutations in the DNMT2 tRNA methyltransferase alter its catalytic properties. Biochimie 2015;112:66–72.
52. Frye M, Dragoni I, Chin SF, Spiteri I, Kurowski A, Provenzano E, et al. Genomic gain of 5p15 leads to over-expression of Misu (NSUN2) in breast cancer. Cancer Lett 2010;289:71–80.
53. Frye M, Watt FM. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr Biol 2006;16:971–81.
54. Hussain S, Benavente SB, Nascimento E, Dragoni I, Kurowski A, Gillich A, et al. The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability. J Cell Biol 2009;186:27–40.
55. Blanco S, Bandiera R, Popis M, Hussain S, Lombard P, Aleksic J, et al. Stem cell function and stress response are controlled by protein synthesis. Nature 2016;534:335–40.
56. Schosserer M, Minois N, Angerer TB, Amring M, Dellago H, Harreither E, et al. Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat Commun 2016;6:6158.
57. Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce SF, Powell CA, et al. Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun 2016;7:12039.
58. Ko M, Huang Y, Jankowska AM, Pape UJ, Tahiliani M, Bandukwala HS, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010;468:839–43.
59. Cimmino L, Dawlaty MM, Ndiaye-Lobry D, Yap YS, Bakogianni S, Yu Y, et al. TET1 is a tumor suppressor of hematopoietic malignancy. Nat Immunol 2015;16:653–62.
60. Chen T, Hao YJ, Zhang Y, Li MM, Wang M, Han W, et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 2015;16:289–301.
61. Little NA, Hastie ND, Davies RC. Identification of WTAP, a novel Wilms’ tumour 1–associating protein. Hum Mol Genet 2000;9: 2231–9.
62. Horiuchi K, Kawamura T, Iwanari H, Ohashi R, Naito M, Kodama T, et al. Identification of Wilms’ tumor 1–associating protein complex and its role in alternative splicing and the cell cycle. J Biol Chem 2013;88:33292–302.
63. Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, et al. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 2015;161:1388–99.
64. Haussmann IU, Bodi Z, Sanchez-Moran E, Mongan NP, Archer N, Fray RG, et al. m6A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination. Nature 2016;540:301–4.
65. Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, Ho CH, et al. m6A modulates neuronal functions and sex determination in Drosophila. Nature 2016;540:242–7.
66. Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, et al. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol Cell 2016;61:507–19.
67. Ma L, Zhao B, Chen K, Thomas A, Tuteja JH, He X, et al. Evolution of transcript modification by N6-methyladenosine in primates. Genome Res 2017;pii: gr.212563.116.
68. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 2011;7:885–7.
69. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ, et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 2013;49:18–29.
70. Iles MM, Law MH, Stacey SN, Han J, Fang S, Pfeiffer R, et al. GenoMEL Consortium; Q–MEGA and AMFS Investigators. A variant in FTO shows association with melanoma risk not due to BMI. Nat Genet 2013;45:428–32.
71. Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, et al. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 2009;85:106–11.
72. Li Z, Weng H, Su R, Weng X, Zuo Z, Li C, et al. FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase. Cancer Cell 2017;31:127–41.
73. Tan A, Dang Y, Chen G, Mo Z. Overexpression of the fat mass and obesity associated gene (FTO) in breast cancer and its clinical implications. Int J Clin Exp Pathol 2015;8:13405–10.
74. Singh B, Kinne HE, Milligan RD, Washburn LJ, Olsen M, Lucci A. Important role of FTO in the survival of rare panresistant triple-negative inflammatory breast cancer cells facing a severe metabolic challenge. PLoS One 2016;11:e0159072.
75. Zhang C, Samanta D, Lu H, Bullen JW, Zhang H, Chen I, et al. Hypoxia induces the breast cancer stem cell phenotype by HIF-dependent and ALKBH5-mediated m6A-demethylation of NANOG mRNA. Proc Natl Acad Sci USA 2016;113:E2047–56.
76. Aas PA, Otterlei M, Falnes PO, Vågbø CB, Skorpen F, Akbar M, et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 2003;421:859–63.
77. Dango S, Mosammaparast N, Sowa ME, Xiong LJ, Wu F, Park K, et al. DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol Cell 2011;44:373–84.
78. Nogales V, Reinhold WC, Varma S, Martinez-Cardus A, Moutinho C, Moran S, et al. Epigenetic inactivation of the putative DNA/RNA helicase SLFN11 in human cancer confers resistance to platinum drugs. Oncotarget 2016;7:3084–97.
79. Ruggero D, Grisendi S, Piazza F, Rego E, Mari F, Rao PH. Dys-keratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 2003;299:259–62.
80. Yoon A, Peng G, Brandenburger Y, Zollo O, Xu W, Rego E, et al. Impaired control of IRES-mediated translation in X-linked dyskera-tosis congenita. Science 2006;312:902–6.
81. Bellodi C, McMahon M, Contreras A, Juliano D, Kopmar N, Nakamura T, et al. H/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation. Cell Rep 2013;3:1493–502.
82. Müller M, Hartmann M, Schuster I, Bender S, Thüring KL, Helm M, et al. Dynamic modulation of Dnmt2-dependent tRNA methylation by the micronutrient queuine. Nucleic Acids Res 2012;43:10952–62.
83. Hagan JP, Piskounova E, Gregory RI. Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells. Nat Struct Mol Biol 2009;16:1021–5.
84. Gruber AJ, Schmidt R, Gruber AR, Martin G, Ghosh S, Belmadani M. A comprehensive analysis of 3′ end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation. Genome Res 2016;26:1145–59.
85. Astuti D, Morris MR, Cooper WN, Staals RH, Wake NC, Fews GA, et al. Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nat Genet 2012;44:277–84.
86. Wetzel C, Limbach PA. Mass spectrometry of modified RNAs: Recent developments. Analyst 2016;141:16–23.
87. Molinie B, Wang J, Lim KS, Hillebrand R, Lu ZX, Van Wittenberghe N, et al. m(6)A–LAIC-seq reveals the census and complexity of the m(6)A epitranscriptome. Nat Methods 2016;13:692–8.
88. Fang G, Munera D, Friedman DI, Mandlik A, Chao MC, Banerjee O, et al. Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nat Biotechnol 2012;30:1232–9.
89. Li S, Mason CE. The pivotal regulatory landscape of RNA modifications. Annu Rev Genomics Hum Genet 2014;15:127–50.
90. Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP, et al. A landscape of pharmacogenomic interactions in cancer. Cell 2016;166: 740–54.
91. Xhemalce B, Robson SC, Kouzarides T. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell 2012;51: 278–8.
92. Begley U, Sosa MS, Avivar-Valderas A, Patil A, Endres L, Estrada Y, et al. A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-α. EMBO Mol Med 2013;5:366–83.
93. Wurm JP, Meyer B, Bahr U, Held M, Frolow O, Kötter P, et al. The ribosome assembly factor Nep1 responsible for Bowen–Conradi syndrome is a pseudouridine–N1-specific methyltransferase. Nucleic Acids Res 2010;38:2387–98.
94. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 2010;142:409–19.
95. Lujambio A, Portela A, Liz J, Melo SA, Rossi S, Spizzo R. CpG island hypermethylation–associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer. Oncogene 2010;29:6390–401.
96. Liz J, Portela A, Soler M, Gómez A, Ling H, Michlewski G. Regulation of pri-miRNA processing by a long noncoding RNA transcribed from an ultraconserved region. Mol Cell 2014;55:138–47.
97. Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP. A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010;465:1033–8.
98. Karreth FA, Reschke M, Ruocco A, Ng C, Chapuy B, Léopold V, et al. The BRAF pseudogene functions as a competitive endogenous RNA and induces lymphoma in vivo. Cell 2015;161:319–32.
99. Feng C, Liu Y, Wang G, Deng Z, Zhang Q, Wu W, et al. Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J Biol Chem 2014;289:11571–83.
100. Xu C, Wang X, Liu K, Roundtree IA, Tempel W, Li Y, et al. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat Chem Biol 2014;10:927–9.
101. Śledź P, Jinek M. Structural insights into the molecular mechanism of the m6A writer complex. Elife 2016;5. pii:e18434.
102. Rodríguez-Paredes M, Esteller M. Cancer epigenetics reaches mainstream oncology. Nat Med 2011;17:330–9.
103. Schaefer M, Hagemann S, Hanna K, Lyko F. Azacytidine inhibits RNA methylation at DNMT2 target sites in human cancer cell lines. Cancer Res 2009;69:8127–32.
104. Khoddami V, Cairns BR. Transcriptome-wide target profiling of RNA cytosine methyltransferases using the mechanism-based enrichment procedure Aza-IP. Nat Protoc 2014;9:337–61.