mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation
Summary: Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcript...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472401489X |
| _version_ | 1826911859905658880 |
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| author | Hideyuki Komori Geeta Rastogi John Paul Bugay Hua Luo Sichun Lin Stephane Angers Craig A. Smibert Howard D. Lipshitz Cheng-Yu Lee |
| author_facet | Hideyuki Komori Geeta Rastogi John Paul Bugay Hua Luo Sichun Lin Stephane Angers Craig A. Smibert Howard D. Lipshitz Cheng-Yu Lee |
| author_sort | Hideyuki Komori |
| collection | DOAJ |
| description | Summary: Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs. Usp5 promotes the formation of the Brat-deadenylase pre-complex in mitotic neural stem cells (neuroblasts) by facilitating Brat interactions with the scaffolding components of deadenylase complexes. The adaptor protein Miranda binds the RNA-binding domain of Brat, limiting its ability to bind target mRNAs in mitotic neuroblasts. Cortical displacement of Miranda activates Brat-deadenylase complex activity in immature INPs. We propose that the assembly of an enzymatically inactive and RNA-binding-deficient pre-complex poises mRNA degradation machineries for rapid activation, driving timely developmental transitions. |
| first_indexed | 2025-02-17T10:21:46Z |
| format | Article |
| id | doaj.art-2d593d2c31e94ca09c258b50ed80cb99 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2025-02-17T10:21:46Z |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2d593d2c31e94ca09c258b50ed80cb992025-01-01T05:10:15ZengElsevierCell Reports2211-12472025-01-01441115138mRNA decay pre-complex assembly drives timely cell-state transitions during differentiationHideyuki Komori0Geeta Rastogi1John Paul Bugay2Hua Luo3Sichun Lin4Stephane Angers5Craig A. Smibert6Howard D. Lipshitz7Cheng-Yu Lee8Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USALife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USADepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, CanadaDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5G 1M1, CanadaDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5G 1M1, CanadaLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Division of Genetic Medicine, Department of Internal Medicine and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Corresponding authorSummary: Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs. Usp5 promotes the formation of the Brat-deadenylase pre-complex in mitotic neural stem cells (neuroblasts) by facilitating Brat interactions with the scaffolding components of deadenylase complexes. The adaptor protein Miranda binds the RNA-binding domain of Brat, limiting its ability to bind target mRNAs in mitotic neuroblasts. Cortical displacement of Miranda activates Brat-deadenylase complex activity in immature INPs. We propose that the assembly of an enzymatically inactive and RNA-binding-deficient pre-complex poises mRNA degradation machineries for rapid activation, driving timely developmental transitions.http://www.sciencedirect.com/science/article/pii/S221112472401489XCP: Developmental biologyCP: Molecular biology |
| spellingShingle | Hideyuki Komori Geeta Rastogi John Paul Bugay Hua Luo Sichun Lin Stephane Angers Craig A. Smibert Howard D. Lipshitz Cheng-Yu Lee mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation Cell Reports CP: Developmental biology CP: Molecular biology |
| title | mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation |
| title_full | mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation |
| title_fullStr | mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation |
| title_full_unstemmed | mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation |
| title_short | mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation |
| title_sort | mrna decay pre complex assembly drives timely cell state transitions during differentiation |
| topic | CP: Developmental biology CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S221112472401489X |
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