Cpeb4-Mediated Translational Regulatory Circuitry Controls Terminal Erythroid Differentiation

Wenqian Hu, Bingbing Yuan, Harvey F. Lodish

Research output: Contribution to journalArticle

25 Scopus citations

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 thatthe 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.

Original languageEnglish (US)
Pages (from-to)660-672
Number of pages13
JournalDevelopmental Cell
Volume30
Issue number6
DOIs
StatePublished - Sep 29 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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