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PMID: 28675155 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The m6A pathway facilitates sex determination in Drosophila.

Nature communications ·Vol. 8 ·2017-00-04 ·Pages 15737

Kan L, Grozhik AV, Vedanayagam J, Patil DP, Pang N, Lim KS, Huang YC, Joseph B, Lin CJ, Despic V, Guo J, Yan D, Kondo S, Deng WM, Dedon PC, Jaffrey SR, Lai EC

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.

MeSH Terms
Adenosine/analogs & derivatives,chemistry Alternative Splicing Amino Acid Motifs Animals Behavior, Animal DNA Methylation Drosophila Proteins/metabolism Drosophila melanogaster/genetics Female Gene Expression Regulation, Developmental Introns Male Mass Spectrometry Models, Genetic Multigene Family Mutagenesis Mutation Ovary/metabolism Phenotype RNA, Messenger/metabolism RNA-Binding Proteins/metabolism Sex Determination Processes Transcriptome
Chemicals
Drosophila Proteins RNA, Messenger RNA-Binding Proteins Sxl protein, Drosophila N-methyladenosine Adenosine
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Kan Lijuan
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Grozhik Anya V
Department of Pharmacology, Weill Medical College, Cornell University, New York City, New York 10065, USA.
Vedanayagam Jeffrey
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Patil Deepak P
Department of Pharmacology, Weill Medical College, Cornell University, New York City, New York 10065, USA.
Pang Nan
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Lim Kok-Seong
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Huang Yi-Chun
Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA.
Joseph Brian
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Lin Ching-Jung
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Despic Vladimir
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
Guo Jian
Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China. | University of Chinese Academy of Sciences, Beijing 100049, China.
Yan Dong
Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
Kondo Shu
Invertebrate Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
Deng Wu-Min
Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA.
Dedon Peter C
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Jaffrey Samie R
Department of Pharmacology, Weill Medical College, Cornell University, New York City, New York 10065, USA.
Lai Eric C
Department of Developmental Biology, Sloan-Kettering Institute, 1275 York Ave, Box 252, New York City, New York 10065, USA.
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms15737
Published
2017-00-04
Epub
2017-00-04
Pages
15737
Language
English
Region
England
NLM ID
101528555
PMCID
PMC5500889
Subset
IM
Grants
NIEHS NIH HHS · R01 ES017010 · United States
NIGMS NIH HHS · R01 GM072562 · United States
NCI NIH HHS · P30 CA008748 · United States
NIEHS NIH HHS · P30 ES002109 · United States
NIDA NIH HHS · R01 DA037150 · United States
NIEHS NIH HHS · R21 ES022858 · United States
NINDS NIH HHS · R01 NS083833 · United States
NINDS NIH HHS · R01 NS074037 · United States
NIGMS NIH HHS · R01 GM083300 · United States
External Links
PubMed source DOI: 10.1038/ncomms15737 PMC Full Text View journal details
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