Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation
While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding pr...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/105473 https://orcid.org/0000-0003-1678-7867 https://orcid.org/0000-0002-7029-7415 |
| _version_ | 1826191146614784000 |
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| author | Yuan, Bingbing Huang, Wenqian Lodish, Harvey F |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Yuan, Bingbing Huang, Wenqian Lodish, Harvey F |
| author_sort | Yuan, Bingbing |
| collection | MIT |
| description | While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. |
| first_indexed | 2024-09-23T08:50:57Z |
| format | Article |
| id | mit-1721.1/105473 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:50:57Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1054732022-09-26T08:45:40Z Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation Yuan, Bingbing Huang, Wenqian Lodish, Harvey F Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Whitehead Institute for Biomedical Research Huang, Wenqian Lodish, Harvey F While we have considerable understanding of the transcriptional networks controlling mammalian cell differentiation, our knowledge of posttranscriptional regulatory events is very limited. Using differentiation of primary erythroid cells as a model, we show that the sequence-specific mRNA-binding protein Cpeb4 is strongly induced by the erythroid-important transcription factors Gata1 and Tal1 and is essential for terminal erythropoiesis. By interacting with the translation initiation factor eIF3, Cpeb4 represses the translation of a large set of mRNAs, including its own mRNA. Thus, transcriptional induction and translational repression combine to form a negative feedback loop to control Cpeb4 protein levels within a specific range that is required for terminal erythropoiesis. Our study provides an example of how translational control is integrated with transcriptional regulation to precisely control gene expression during mammalian cell differentiation. Life Sciences Research Foundation (Merck Fellow) National Institutes of Health (U.S.) (Pathway to Independence Award (1K99HL118157)) National Institutes of Health (U.S.) (NIH grant R01DK068348) National Institutes of Health (U.S.) (NIH grant 5P01HL066105) 2016-11-30T16:14:34Z 2016-11-30T16:14:34Z 2014-09 2014-06 Article http://purl.org/eprint/type/JournalArticle 15345807 http://hdl.handle.net/1721.1/105473 Hu, Wenqian, Bingbing Yuan, and Harvey F. Lodish. “Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation.” Developmental Cell 30, no. 6 (September 2014): 660–672. https://orcid.org/0000-0003-1678-7867 https://orcid.org/0000-0002-7029-7415 en_US http://dx.doi.org/10.1016/j.devcel.2014.07.008 Developmental Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Yuan, Bingbing Huang, Wenqian Lodish, Harvey F Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title | Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title_full | Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title_fullStr | Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title_full_unstemmed | Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title_short | Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation |
| title_sort | cpeb4 mediated translational regulatory circuitry controls terminal erythroid differentiation |
| url | http://hdl.handle.net/1721.1/105473 https://orcid.org/0000-0003-1678-7867 https://orcid.org/0000-0002-7029-7415 |
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