The m⁶A Pathway Facilitates Sex Determination in Drosophila
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ncomms15737.pdf
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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
Date Issued
July 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Kan, Lijuan et al. “The m⁶A Pathway Facilitates Sex Determination in Drosophila.” Nature Communications 8 (July 2017): 15737 © 2017 The Author(s)
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/NCOMMS15737
