MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1

Dinesh S. Rao, Ryan M. O'Connell, Aadel A. Chaudhuri, Yvette Garcia-Flores, Theresa L. Geiger, David Baltimore

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

MicroRNAs (miRNAs) can influence lineage choice or affect critical developmental checkpoints during hematopoiesis. We examined the role of the p53-induced microRNA miR-34a in hematopoiesis by gain-of-function analysis in murine bone marrow. Constitutive expression of miR-34a led to a block in B cell development at the pro-B-cell-to-pre-B-cell transition, leading to a reduction in mature B cells. This block appeared to be mediated primarily by inhibited expression of the transcription factor Foxp1. Foxp1 was a direct target of miR-34a in a 3. '-untranslated region (UTR)-dependent fashion. Knockdown of Foxp1 by siRNA recapitulated the B cell developmental phenotype induced by miR-34a, whereas cotransduction of Foxp1 lacking its 3. ' UTR with miR-34a rescued B cell maturation. Knockdown of miR-34a resulted in increased amounts of Foxp1 and mature B cells. These findings identify a role for miR-34a in connecting the p53 network with suppression of Foxp1, a known B cell oncogene.

Original languageEnglish
Pages (from-to)48-59
Number of pages12
JournalImmunity
Volume33
Issue number1
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Keywords

  • Cellimmuno
  • Molimmuno

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