The m(6)A pathway facilitates sex determination in Drosophila Journal Article
| Authors: | Kan, L.; Grozhik, A. V.; Vedanayagam, J.; Patil, D. P.; Pang, N.; Lim, K. S.; Huang, Y. C.; Joseph, B.; Lin, C. J.; Despic, V.; Guo, J.; Yan, D.; Kondo, S.; Deng, W. M.; Dedon, P. C.; Jaffrey, S. R.; Lai, E. C. |
| Article Title: | The m(6)A pathway facilitates sex determination in Drosophila |
| Abstract: | The conserved modification N 6 -methyladenosine (m 6 A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the m 6 A pathway. We first apply miCLIP to map m 6 A across embryogenesis, characterize its m 6 A 'writer' complex, validate its YTH 'readers' CG6422 and YT521-B, and generate mutants in five m 6 A factors. While m 6 A factors with additional roles in splicing are lethal, m 6 A-specific mutants are viable but present certain developmental and behavioural defects. Notably, m 6 A facilitates the master female determinant Sxl, since multiple m 6 A components enhance female lethality in Sxl sensitized backgrounds. The m 6 A pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic m 6 A target, and female-specific Sxl splicing is compromised in multiple m 6 A pathway mutants. YT521-B is a dominant m 6 A effector for Sxl regulation, and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit reveals in vivo biologic function for the Drosophila m 6 A pathway. |
| Journal Title: | Nature Communications |
| Volume: | 8 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-07-04 |
| Start Page: | 15737 |
| Language: | English |
| DOI: | 10.1038/ncomms15737 |
| PROVIDER: | scopus |
| PMCID: | PMC5500889 |
| PUBMED: | 28675155 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
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