The m6A pathway facilitates sex determination in Drosophila

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...

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Published in:Nature communications 2017-07, Vol.8 (1), p.15737-16, Article 15737
Main Authors: Kan, Lijuan, Grozhik, Anya V., Vedanayagam, Jeffrey, Patil, Deepak P., Pang, Nan, Lim, Kok-Seong, Huang, Yi-Chun, Joseph, Brian, Lin, Ching-Jung, Despic, Vladimir, Guo, Jian, Yan, Dong, Kondo, Shu, Deng, Wu-Min, Dedon, Peter C., Jaffrey, Samie R., Lai, Eric C.
Format: Article
Language:English
Subjects:
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Defects
Drosophila
Embryogenesis
Embryonic growth stage
Humanities and Social Sciences
Insects
Lethality
mRNA processing
multidisciplinary
Mutants
N6-methyladenosine
Readers
Science
Science (multidisciplinary)
Sex determination
Splicing
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Summary: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. N 6 -methyladenosine (m 6 A) is a conserved RNA modification that has recently emerged as an important regulator of messenger RNA processing and activity. Here, the authors provide evidence that m6A pathway facilitates female-specific splicing of Sxl , regulating sex determination in Drosophila .
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms15737