The m⁶A Pathway Facilitates Sex Determination in Drosophila
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'...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/113617 https://orcid.org/0000-0003-0011-3067 |
| _version_ | 1811072490120675328 |
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| author | Kan, Lijuan Grozhik, Anya V. Vedanayagam, Jeffrey Patil, Deepak P. Pang, Nan Huang, Yi-Chun Joseph, Brian Lin, Ching-Jung Despic, Vladimir Guo, Jian Yan, Dong Kondo, Shu Deng, Wu-Min Jaffrey, Samie R. Lai, Eric C. Lim, Kok Seong Dedon, Peter C |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Kan, Lijuan Grozhik, Anya V. Vedanayagam, Jeffrey Patil, Deepak P. Pang, Nan Huang, Yi-Chun Joseph, Brian Lin, Ching-Jung Despic, Vladimir Guo, Jian Yan, Dong Kondo, Shu Deng, Wu-Min Jaffrey, Samie R. Lai, Eric C. Lim, Kok Seong Dedon, Peter C |
| author_sort | Kan, Lijuan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:06:47Z |
| format | Article |
| id | mit-1721.1/113617 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:06:47Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1136172022-09-30T13:31:24Z The m⁶A Pathway Facilitates Sex Determination in Drosophila Kan, Lijuan Grozhik, Anya V. Vedanayagam, Jeffrey Patil, Deepak P. Pang, Nan Huang, Yi-Chun Joseph, Brian Lin, Ching-Jung Despic, Vladimir Guo, Jian Yan, Dong Kondo, Shu Deng, Wu-Min Jaffrey, Samie R. Lai, Eric C. Lim, Kok Seong Dedon, Peter C Massachusetts Institute of Technology. Department of Biological Engineering Lim, Kok Seong Dedon, Peter C 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. 2018-02-13T14:26:20Z 2018-02-13T14:26:20Z 2017-07 2016-12 2018-02-09T15:56:26Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/113617 Kan, Lijuan et al. “The m⁶A Pathway Facilitates Sex Determination in Drosophila.” Nature Communications 8 (July 2017): 15737 © 2017 The Author(s) https://orcid.org/0000-0003-0011-3067 http://dx.doi.org/10.1038/NCOMMS15737 Nature Communications Creative Commons Attribution 4.0 International License https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group |
| spellingShingle | Kan, Lijuan Grozhik, Anya V. Vedanayagam, Jeffrey Patil, Deepak P. Pang, Nan Huang, Yi-Chun Joseph, Brian Lin, Ching-Jung Despic, Vladimir Guo, Jian Yan, Dong Kondo, Shu Deng, Wu-Min Jaffrey, Samie R. Lai, Eric C. Lim, Kok Seong Dedon, Peter C The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title | The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title_full | The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title_fullStr | The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title_full_unstemmed | The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title_short | The m⁶A Pathway Facilitates Sex Determination in Drosophila |
| title_sort | m⁶a pathway facilitates sex determination in drosophila |
| url | http://hdl.handle.net/1721.1/113617 https://orcid.org/0000-0003-0011-3067 |
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