The m(6)A 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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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500889/
https://www.ncbi.nlm.nih.gov/pubmed/28675155
http://dx.doi.org/10.1038/ncomms15737
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author 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.
author_facet 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.
author_sort Kan, Lijuan
collection PubMed
description 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.
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spelling pubmed-55008892017-07-11 The m(6)A pathway facilitates sex determination in Drosophila 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. Nat Commun Article 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. Nature Publishing Group 2017-07-04 /pmc/articles/PMC5500889/ /pubmed/28675155 http://dx.doi.org/10.1038/ncomms15737 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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.
The m(6)A pathway facilitates sex determination in Drosophila
title The m(6)A pathway facilitates sex determination in Drosophila
title_full The m(6)A pathway facilitates sex determination in Drosophila
title_fullStr The m(6)A pathway facilitates sex determination in Drosophila
title_full_unstemmed The m(6)A pathway facilitates sex determination in Drosophila
title_short The m(6)A pathway facilitates sex determination in Drosophila
title_sort m(6)a pathway facilitates sex determination in drosophila
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500889/
https://www.ncbi.nlm.nih.gov/pubmed/28675155
http://dx.doi.org/10.1038/ncomms15737
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