The m⁶A Pathway Facilitates Sex Determination in Drosophila
Author(s)Kan, Lijuan; Grozhik, Anya V.; Vedanayagam, Jeffrey; Patil, Deepak P.; Pang, Nan; Huang, Yi-Chun; Joseph, Brian; Lin, Ching-Jung; Despic, Vladimir; Guo, Jian; Yan, Dong; Kondo, Shu; Deng, Wu-Min; Jaffrey, Samie R.; Lai, Eric C.; Lim, Kok Seong; Dedon, Peter C; ... Show more Show less
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The conserved modification N⁶-methyladenosine (m⁶A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the m⁶A pathway. We first apply miCLIP to map m 6 A across embryogenesis, characterize its m⁶A 'writer' complex, validate its YTH 'readers' CG6422 and YT521-B, and generate mutants in five m⁶A factors. While m⁶A factors with additional roles in splicing are lethal, m⁶A-specific mutants are viable but present certain developmental and behavioural defects. Notably, m⁶A facilitates the master female determinant Sxl, since multiple m⁶A components enhance female lethality in Sxl sensitized backgrounds. The m⁶A pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic m⁶A target, and female-specific Sxl splicing is compromised in multiple m⁶A pathway mutants. YT521-B is a dominant m⁶A 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 m⁶A pathway.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering
Nature Publishing Group
Kan, Lijuan et al. “The m⁶A Pathway Facilitates Sex Determination in Drosophila.” Nature Communications 8 (July 2017): 15737 © 2017 The Author(s)
Final published version