The m6A Methyltransferase METTL3 Promotes Translation in Human Cancer Cells

Molecular Cell

Volumn 62, Issue 3, 2016, Pages 335-345

  Lin, Shuibin ^a,b   Choe, Junho ^a,b   Du, Peng ^a,b   Triboulet, Robinson ^a,b   Gregory, Richard I ^a,b,c  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

Cancer; EGFR; M6A; METTL3; N6 methyladenosine; Ribosome; Translation

Indexed keywords

EPIDERMAL GROWTH FACTOR RECEPTOR; RNA METHYLTRANSFERASE; RNA METHYLTRANSFERASE METTL3; UNCLASSIFIED DRUG; EGFR PROTEIN, HUMAN; INITIATION FACTOR 3; MESSENGER RNA; METHYLTRANSFERASE; METTL3 PROTEIN, HUMAN; SIGNAL PEPTIDE; WWTR1 PROTEIN, HUMAN;

ARTICLE; CANCER CELL; CANCER GROWTH; CANCER SURVIVAL; CATALYSIS; CONTROLLED STUDY; GAIN OF FUNCTION MUTATION; HUMAN; HUMAN CELL; LOSS OF FUNCTION MUTATION; LUNG ADENOCARCINOMA; PROTEIN EXPRESSION; RIBOSOME; RNA TRANSLATION; TRANSLATION INITIATION; TUMOR INVASION; A-549 CELL LINE; ADENOCARCINOMA; BIOSYNTHESIS; CELL MOTION; CELL PROLIFERATION; CELL SURVIVAL; ENZYMOLOGY; GENE EXPRESSION REGULATION; GENETIC TRANSFECTION; GENETICS; LUNG TUMOR; METABOLISM; PATHOLOGY; RNA INTERFERENCE; SIGNAL TRANSDUCTION; UPREGULATION;

A549 CELLS; ADENOCARCINOMA; CELL MOVEMENT; CELL PROLIFERATION; CELL SURVIVAL; EUKARYOTIC INITIATION FACTOR-3; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LUNG NEOPLASMS; METHYLTRANSFERASES; NEOPLASM INVASIVENESS; PEPTIDE CHAIN INITIATION, TRANSLATIONAL; RECEPTOR, EPIDERMAL GROWTH FACTOR; RIBOSOMES; RNA INTERFERENCE; RNA, MESSENGER; SIGNAL TRANSDUCTION; TRANSFECTION; UP-REGULATION;

EID: 84963983880     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2016.03.021     Document Type: Article

References (46)

1. Alarcón C.R., Goodarzi H., Lee H., Liu X., Tavazoie S., Tavazoie S.F. HNRNPA2B1 is a mediator of m(6)a-dependent nuclear RNA processing events. Cell 2015, 162:1299-1308.
2. Alarcón C.R., Lee H., Goodarzi H., Halberg N., Tavazoie S.F. N6-methyladenosine marks primary microRNAs for processing. Nature 2015, 519:482-485.
3. Batista P.J., Molinie B., Wang J., Qu K., Zhang J., Li L., Bouley D.M., Lujan E., Haddad B., Daneshvar K., et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 2014, 15:707-719.
4. Bokar J.A., Shambaugh M.E., Polayes D., Matera A.G., Rottman F.M. Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 1997, 3:1233-1247.
5. Chang H.M., Martinez N.J., Thornton J.E., Hagan J.P., Nguyen K.D., Gregory R.I. Trim71 cooperates with microRNAs to repress Cdkn1a expression and promote embryonic stem cell proliferation. Nat. Commun. 2012, 3:923.
6. Chen T., Hao Y.J., Zhang Y., Li M.M., Wang M., Han W., Wu Y., Lv Y., Hao J., Wang L., et al. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell 2015, 16:289-301.
7. Choe J., Oh N., Park S., Lee Y.K., Song O.K., Locker N., Chi S.G., Kim Y.K. Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g. J. Biol. Chem. 2012, 287:18500-18509.
8. Desrosiers R., Friderici K., Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc. Natl. Acad. Sci. USA 1974, 71:3971-3975.
9. Dominissini D., Moshitch-Moshkovitz S., Schwartz S., Salmon-Divon M., Ungar L., Osenberg S., Cesarkas K., Jacob-Hirsch J., Amariglio N., Kupiec M., et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012, 485:201-206.
10. Dominissini D., Moshitch-Moshkovitz S., Salmon-Divon M., Amariglio N., Rechavi G. Transcriptome-wide mapping of N(6)-methyladenosine by m(6)A-seq based on immunocapturing and massively parallel sequencing. Nat. Protoc. 2013, 8:176-189.
11. Fustin J.M., Doi M., Yamaguchi Y., Hida H., Nishimura S., Yoshida M., Isagawa T., Morioka M.S., Kakeya H., Manabe I., Okamura H. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell 2013, 155:793-806.
12. Gao X., Wan J., Liu B., Ma M., Shen B., Qian S.B. Quantitative profiling of initiating ribosomes in vivo. Nat. Methods 2015, 12:147-153.
13. Garcia-Closas M., Couch F.J., Lindstrom S., Michailidou K., Schmidt M.K., Brook M.N., Orr N., Rhie S.K., Riboli E., Feigelson H.S., et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat. Genet. 2013, 45:392-398. 398e391-392.
14. Geula S., Moshitch-Moshkovitz S., Dominissini D., Mansour A.A., Kol N., Salmon-Divon M., Hershkovitz V., Peer E., Mor N., Manor Y.S., et al. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 2015, 347:1002-1006.
15. Harper J.E., Miceli S.M., Roberts R.J., Manley J.L. Sequence specificity of the human mRNA N6-adenosine methylase in vitro. Nucleic Acids Res. 1990, 18:5735-5741.
16. Heilman K.L., Leach R.A., Tuck M.T. Internal 6-methyladenine residues increase the in vitro translation efficiency of dihydrofolate reductase messenger RNA. Int. J. Biochem. Cell Biol. 1996, 28:823-829.
17. Horowitz S., Horowitz A., Nilsen T.W., Munns T.W., Rottman F.M. Mapping of N6-methyladenosine residues in bovine prolactin mRNA. Proc. Natl. Acad. Sci. USA 1984, 81:5667-5671.
18. Iles M.M., Law M.H., Stacey S.N., Han J., Fang S., Pfeiffer R., Harland M., Macgregor S., Taylor J.C., Aben K.K., et al. A variant in FTO shows association with melanoma risk not due to BMI. Nat. Genet. 2013, 45:428-432. 432e421.
19. Jia G., Fu Y., Zhao X., Dai Q., Zheng G., Yang Y., Yi C., Lindahl T., Pan T., Yang Y.G., He C. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 2011, 7:885-887.
20. Ke S., Alemu E.A., Mertens C., Gantman E.C., Fak J.J., Mele A., Haripal B., Zucker-Scharff I., Moore M.J., Park C.Y., et al. A majority of m6A residues are in the last exons, allowing the potential for 3' UTR regulation. Genes Dev. 2015, 29:2037-2053.
21. Kim K.M., Cho H., Choi K., Kim J., Kim B.W., Ko Y.G., Jang S.K., Kim Y.K. A new MIF4G domain-containing protein, CTIF, directs nuclear cap-binding protein CBP80/20-dependent translation. Genes Dev. 2009, 23:2033-2045.
22. Li F., Zhao D., Wu J., Shi Y. Structure of the YTH domain of human YTHDF2 in complex with an m(6)A mononucleotide reveals an aromatic cage for m(6)A recognition. Cell Res. 2014, 24:1490-1492.
23. Lin S., Gregory R.I. Methyltransferases modulate RNA stability in embryonic stem cells. Nat. Cell Biol. 2014, 16:129-131.
24. Liu J., Yue Y., Han D., Wang X., Fu Y., Zhang L., Jia G., Yu M., Lu Z., Deng X., et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 2014, 10:93-95.
25. Liu N., Dai Q., Zheng G., He C., Parisien M., Pan T. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 2015, 518:560-564.
26. Meyer K.D., Jaffrey S.R. The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat. Rev. Mol. Cell Biol. 2014, 15:313-326.
27. Meyer K.D., Saletore Y., Zumbo P., Elemento O., Mason C.E., Jaffrey S.R. Comprehensive analysis of mRNA methylation reveals enrichment in 3' UTRs and near stop codons. Cell 2012, 149:1635-1646.
28. Meyer K.D., Patil D.P., Zhou J., Zinoviev A., Skabkin M.A., Elemento O., Pestova T.V., Qian S.B., Jaffrey S.R. 5' UTR m(6)A promotes cap-independent translation. Cell 2015, 163:999-1010.
29. Oh N., Kim K.M., Cho H., Choe J., Kim Y.K. Pioneer round of translation occurs during serum starvation. Biochem. Biophys. Res. Commun. 2007, 362:145-151.
30. Perry R.P., Kelley D.E., Friderici K., Rottman F. The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5' terminus. Cell 1975, 4:387-394.
31. Ping X.L., Sun B.F., Wang L., Xiao W., Yang X., Wang W.J., Adhikari S., Shi Y., Lv Y., Chen Y.S., et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014, 24:177-189.
32. Schwartz S., Mumbach M.R., Jovanovic M., Wang T., Maciag K., Bushkin G.G., Mertins P., Ter-Ovanesyan D., Habib N., Cacchiarelli D., et al. Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5' sites. Cell Rep. 2014, 8:284-296.
33. Theler D., Dominguez C., Blatter M., Boudet J., Allain F.H. Solution structure of the YTH domain in complex with N6-methyladenosine RNA: a reader of methylated RNA. Nucleic Acids Res. 2014, 42:13911-13919.
34. Tuck M.T. Partial purification of a 6-methyladenine mRNA methyltransferase which modifies internal adenine residues. Biochem. J. 1992, 288:233-240.
35. Tuck M.T., James C.B., Kelder B., Kopchick J.J. Elevation of internal 6-methyladenine mRNA methyltransferase activity after cellular transformation. Cancer Lett. 1996, 103:107-113.
36. Wang L.N., Wang Y., Lu Y., Yin Z.F., Zhang Y.H., Aslanidi G.V., Srivastava A., Ling C.Q., Ling C. Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo. J. Integr. Med. 2014, 12:20-34.
37. Wang X., Lu Z., Gomez A., Hon G.C., Yue Y., Han D., Fu Y., Parisien M., Dai Q., Jia G., et al. N6-methyladenosine-dependent regulation of messenger RNA stability. Nature 2014, 505:117-120.
38. Wang Y., Li Y., Toth J.I., Petroski M.D., Zhang Z., Zhao J.C. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol. 2014, 16:191-198.
39. Wang X., Zhao B.S., Roundtree I.A., Lu Z., Han D., Ma H., Weng X., Chen K., Shi H., He C. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell 2015, 161:1388-1399.
40. Xu C., Wang X., Liu K., Roundtree I.A., Tempel W., Li Y., Lu Z., He C., Min J. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain. Nat. Chem. Biol. 2014, 10:927-929.
41. Yue Y., Liu J., He C. RNA N6-methyladenosine methylation in post-transcriptional gene expression regulation. Genes Dev. 2015, 29:1343-1355.
42. Zhang Y.H., Wang Y., Yusufali A.H., Ashby F., Zhang D., Yin Z.F., Aslanidi G.V., Srivastava A., Ling C.Q., Ling C. Cytotoxic genes from traditional Chinese medicine inhibit tumor growth both in vitro and in vivo. J. Integr. Med. 2014, 12:483-494.
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., et al. FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis. Cell Res. 2014, 24:1403-1419.
44. Zheng G., Dahl J.A., Niu Y., Fedorcsak P., Huang C.M., Li C.J., Vågbø C.B., Shi Y., Wang W.L., Song S.H., et al. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 2013, 49:18-29.
45. Zhou J., Wan J., Gao X., Zhang X., Jaffrey S.R., Qian S.B. Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature 2015, 526:591-594.
46. Zhu T., Roundtree I.A., Wang P., Wang X., Wang L., Sun C., Tian Y., Li J., He C., Xu Y. Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Res. 2014, 24:1493-1496.