The exosome complex establishes a barricade to erythroid maturation

Skye C. McIver, Yoon A. Kang, Andrew W. Devilbiss, Chelsea A. O'Driscoll, Jonathan N. Ouellette, Nathaniel J. Pope, Genis Camprecios, Chan Jung Chang, David Yang, Eric E. Bouhassira, Saghi Ghaffari, Emery H. Bresnick

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Complex genetic networks control hematopoietic stem cell differentiation into progenitors that give rise to billions of erythrocytes daily. Previously, we described a role for the master regulator of erythropoiesis, GATA-1, in inducing genes encoding components of the autophagy machinery. In this context, the Forkhead transcription factor, Foxo3, amplified GATA-1-mediated transcriptional activation. To determine the scope of the GATA-1/Foxo3 cooperativity, and to develop functional insights, we analyzed the GATA-1/Foxo3-dependent transcriptome in erythroid cells. GATA-1/Foxo3 repressed expression of Exosc8, a pivotal component of the exosome complex, which mediates RNA surveillance and epigenetic regulation. Strikingly, downregulating Exosc8, or additional exosome complex components, in primary erythroid precursor cells induced erythroid cell maturation. Our results demonstrate a new mode of controlling erythropoiesis in which multiple components of the exosome complex are endogenous suppressors of the erythroid developmental program. (Blood. 2014;124(14):2285-2297).

Original languageEnglish (US)
Pages (from-to)2285-2297
Number of pages13
JournalBlood
Volume124
Issue number14
DOIs
StatePublished - Oct 2 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    McIver, S. C., Kang, Y. A., Devilbiss, A. W., O'Driscoll, C. A., Ouellette, J. N., Pope, N. J., Camprecios, G., Chang, C. J., Yang, D., Bouhassira, E. E., Ghaffari, S., & Bresnick, E. H. (2014). The exosome complex establishes a barricade to erythroid maturation. Blood, 124(14), 2285-2297. https://doi.org/10.1182/blood-2014-04-571083