Author
Listed:
- Lijuan Kan
(Sloan-Kettering Institute)
- Anya V. Grozhik
(Weill Medical College, Cornell University)
- Jeffrey Vedanayagam
(Sloan-Kettering Institute)
- Deepak P. Patil
(Weill Medical College, Cornell University)
- Nan Pang
(Sloan-Kettering Institute)
- Kok-Seong Lim
(Massachusetts Institute of Technology)
- Yi-Chun Huang
(Florida State University)
- Brian Joseph
(Sloan-Kettering Institute)
- Ching-Jung Lin
(Sloan-Kettering Institute)
- Vladimir Despic
(Sloan-Kettering Institute)
- Jian Guo
(Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
University of Chinese Academy of Sciences)
- Dong Yan
(Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences)
- Shu Kondo
(Invertebrate Genetics Laboratory, National Institute of Genetics)
- Wu-Min Deng
(Florida State University)
- Peter C. Dedon
(Massachusetts Institute of Technology)
- Samie R. Jaffrey
(Weill Medical College, Cornell University)
- Eric C. Lai
(Sloan-Kettering Institute)
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 m6A 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.
Suggested Citation
Lijuan Kan & Anya V. Grozhik & Jeffrey Vedanayagam & Deepak P. Patil & Nan Pang & Kok-Seong Lim & Yi-Chun Huang & Brian Joseph & Ching-Jung Lin & Vladimir Despic & Jian Guo & Dong Yan & Shu Kondo & Wu, 2017.
"The m6A pathway facilitates sex determination in Drosophila,"
Nature Communications, Nature, vol. 8(1), pages 1-16, August.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15737
DOI: 10.1038/ncomms15737
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