Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation
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Lodish_cpeb4.pdf
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2.78 MB
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Author(s)
Yuan, Bingbing
Huang, Wenqian
Lodish, Harvey F
Date Issued
September 2014
Journal
Developmental Cell
Publisher
Elsevier
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
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
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2014.07.008
