M6 A potentiates Sxl alternative pre-mRNA splicing for robust Drosophila sex determination

Nature

Volumn 540, Issue 7632, 2016, Pages 301-304

  Haussmann, Irmgard U ^a,b   Bodi, Zsuzsanna ^c   Sanchez Moran, Eugenio ^a   Mongan, Nigel P ^c   Archer, Nathan ^c   Fray, Rupert G ^c   Soller, Matthias ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b Institute for Clean Growth and Future Mobility   (United Kingdom)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

6 N METHYLADENOSINE; MESSENGER RNA; RNA BINDING PROTEIN; SXL PROTEIN; UNCLASSIFIED DRUG; 5' UNTRANSLATED REGION; ADENOSINE; DNA BINDING PROTEIN; DROSOPHILA PROTEIN; IME4 PROTEIN, DROSOPHILA; METHYLTRANSFERASE; MSL-2 PROTEIN, DROSOPHILA; N(6)-METHYLADENOSINE; NUCLEAR PROTEIN; RNA PRECURSOR; SXL PROTEIN, DROSOPHILA; TRANSCRIPTION FACTOR; YT521-B PROTEIN, DROSOPHILA;

ENZYME ACTIVITY; FLY; GENE EXPRESSION; PROTEIN; RNA; SEX DETERMINATION; TUMOR;

5' UNTRANSLATED REGION; ALTERNATIVE RNA SPLICING; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DROSOPHILA; FEMALE; GENE EXPRESSION REGULATION; GENE LOSS; GENE REPRESSION; INTRON; MALE; NONHUMAN; PRIORITY JOURNAL; SEX DETERMINATION; ANALOGS AND DERIVATIVES; ANIMAL; BIOSYNTHESIS; CHEMISTRY; DEFICIENCY; DROSOPHILA MELANOGASTER; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; NERVE CELL; SEX DETERMINATION PROCESS; SEXUAL DEVELOPMENT;

EUKARYOTA; MAMMALIA; VIR;

5' UNTRANSLATED REGIONS; ADENOSINE; ALTERNATIVE SPLICING; ANIMALS; DNA-BINDING PROTEINS; DOSAGE COMPENSATION, GENETIC; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; FEMALE; INTRONS; MALE; METHYLTRANSFERASES; NEURONS; NUCLEAR PROTEINS; RNA PRECURSORS; RNA, MESSENGER; RNA-BINDING PROTEINS; SEX CHARACTERISTICS; SEX DETERMINATION PROCESSES; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 85017163153     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature20577     Document Type: Article

References (42)

1. Luo, S. & Tong, L. Molecular basis for the recognition of methylated adenines in RNA by the eukaryotic YTH domain. Proc. Natl Acad. Sci. USA 111, 13834-13839 (2014).
2. Meyer, K. D. et al. Comprehensive analysis of mRNA methylation reveals enrichment in 3′ UTRs and near stop codons. Cell 149, 1635-1646 (2012).
3. Dominissini, D. et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 485, 201-206 (2012).
4. Perry, R. P. & Kelley, D. E. Existence of methylated messenger RNA in mouse L cells. Cell 1, 37-42 (1974).
5. Zhong, S. et al. MTA is an Arabidopsis messenger RNA adenosine methylase and interacts with a homolog of a sex-specific splicing factor. Plant Cell 20, 1278-1288 (2008).
6. Schwartz, S. et al. High-resolution mapping reveals a conserved, widespread, dynamic mRNA methylation program in yeast meiosis. Cell 155, 1409-1421 (2013).
7. Ke, S. et al. A majority of m6A residues are in the last exons, allowing the potential for 3′ UTR regulation. Genes Dev. 29, 2037-2053 (2015).
8. Liu, J. et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10, 93-95 (2014).
9. Horiuchi, K. et al. Identification of Wilms' tumor 1-associating protein complex and its role in alternative splicing and the cell cycle. J. Biol. Chem. 288, 33292-33302 (2013).
10. 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 3, 1233-1247 (1997).
11. Penalva, L. O. et al. The Drosophila fl(2)d gene, required for female-specific splicing of Sxl and tra pre-mRNAs, encodes a novel nuclear protein with a HQ-rich domain. Genetics 155, 129-139 (2000).
12. Niessen, M., Schneiter, R. & Nothiger, R. Molecular identification of virilizer, a gene required for the expression of the sex-determining gene Sex-lethal in Drosophila melanogaster. Genetics 157, 679-688 (2001).
13. Schütt, C. & Nöthiger, R. Structure, function and evolution of sex-determining systems in Dipteran insects. Development 127, 667-677 (2000).
14. Geula, S. et al. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation. Science 347, 1002-1006 (2015).
15. Luo, G. Z. et al. Unique features of the m6A methylome in Arabidopsis thaliana. Nat. Commun. 5, 5630 (2014).
16. Xiao, W. et al. Nuclear m6A reader YTHDC1 regulates mRNA splicing. Mol. Cell 61, 507-519 (2016).
17. Hongay, C. F. & Orr-Weaver, T. L. Drosophila Inducer of MEiosis 4 (IME4) is required for Notch signaling during oogenesis. Proc. Natl Acad. Sci. USA 108, 14855-14860 (2011).
18. Bodi, Z., Bottley, A., Archer, N., May, S. T. & Fray, R. G. Yeast m6A methylated mRNAs are enriched on translating ribosomes during meiosis, and under rapamycin treatment. PLoS One 10, e0132090 (2015).
19. Wang, X. et al. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 161, 1388-1399 (2015).
20. Meyer, K. D. et al. 5′ UTR m6A Promotes Cap-Independent Translation. Cell 163, 999-1010 (2015).
21. Zhou, J. et al. Dynamic m6A mRNA methylation directs translational control of heat shock response. Nature 526, 591-594 (2015).
22. Zaharieva, E., Haussmann, I. U., Bräuer, U. & Soller, M. Concentration and localization of co-expressed ELAV/Hu proteins control specificity of mRNA processing. Mol. Cell. Biol. 35, 3104-3115 (2015).
23. Salz, H. K. Sex, stem cells and tumors in the Drosophila ovary. Fly (Austin) 7, 3-7 (2013).
24. Bodi, Z., Button, J. D., Grierson, D. & Fray, R. G. Yeast targets for mRNA methylation. Nucleic Acids Res. 38, 5327-5335 (2010).
25. Hilfiker, A., Amrein, H., Dübendorfer, A., Schneiter, R. & Nöthiger, R. The gene virilizer is required for female-specific splicing controlled by Sxl, the master gene for sexual development in Drosophila. Development 121, 4017-4026 (1995).
26. Starck, S. R. et al. Translation from the 5′ untranslated region shapes the integrated stress response. Science 351, aad3867 (2016).
27. Church, C. et al. Overexpression of Fto leads to increased food intake and results in obesity. Nat. Genet. 42, 1086-1092 (2010).
28. Moindrot, B. et al. A pooled shRNA screen identifies Rbm15, Spen, and Wtap as factors required for Xist RNA-mediated silencing. Cell Reports 12, 562-572 (2015).
29. Patil, D. P. et al. m6A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537, 369-373 (2016).
30. Haussmann, I. U., Hemani, Y., Wijesekera, T., Dauwalder, B. & Soller, M. Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila reproductive behaviours. Proc. R. Soc. Lond. B 280, 20131938 (2013).
31. Haussmann, I. U., Li, M. & Soller, M. ELAV-mediated 3′-end processing of ewg transcripts is evolutionarily conserved despite sequence degeneration of the ELAV-binding site. Genetics 189, 97-107 (2011).
32. Yan, D. & Perrimon, N. spenito is required for sex determination in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 112, 11606-11611 (2015).
33. Livak, K. J. & Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25, 402-408 (2001).
34. Haussmann, I. U., White, K. & Soller, M. Erect wing regulates synaptic growth in Drosophila by integration of multiple signaling pathways. Genome Biol. 9, R73 (2008).
35. Soller, M. & White, K. ELAV inhibits 3′-end processing to promote neural splicing of ewg pre-mRNA. Genes Dev. 17, 2526-2538 (2003).
36. 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. 18, 5735-5741 (1990).
37. Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).
38. Trapnell, C. et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protocols 7, 562-578 (2012).
39. Sturgill, D. et al. Design of RNA splicing analysis null models for post hoc filtering of Drosophila head RNA-seq data with the splicing analysis kit (Spanki). BMC Bioinformatics 14, 320 (2013).
40. Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24-26 (2011).
41. Soller, M., Bownes, M. & Kubli, E. Control of oocyte maturation in sexually mature Drosophila females. Dev. Biol. 208, 337-351 (1999).
42. Soller, M. & White, K. ELAV multimerizes on conserved AU4-6 motifs important for ewg splicing regulation. Mol. Cell. Biol. 25, 7580-7591 (2005).