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PMID: 20598588 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Immunity ·Vol. 33 ·No. 1 ·2010-07-23 ·Pages 48-59

Rao DS, O'Connell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore D

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.

MeSH Terms
3' Untranslated Regions Animals B-Lymphocytes/metabolism,pathology Bone Marrow/metabolism,pathology Cell Line Cloning, Molecular Forkhead Transcription Factors/genetics,metabolism Hematopoiesis Humans Mice Mice, Inbred C57BL MicroRNAs/genetics Precursor Cells, B-Lymphoid/metabolism,pathology Radiation Chimera Repressor Proteins/genetics,metabolism Tumor Suppressor Protein p53/metabolism
Chemicals
3' Untranslated Regions FOXP1 protein, human Forkhead Transcription Factors MIRN34 microRNA, human MicroRNAs Repressor Proteins Tumor Suppressor Protein p53
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rao Dinesh S
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
O'Connell Ryan M
Chaudhuri Aadel A
Garcia-Flores Yvette
Geiger Theresa L
Baltimore David
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2010.06.013
Published
2010-07-23
Epub
2010-00-01
Pages
48-59
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2911227
Subset
IM
Grants
NHLBI NIH HHS · K99 HL102228-02 · United States
NCI NIH HHS · K08 CA133521 · United States
NCI NIH HHS · 1K08CA133521 · United States
NCI NIH HHS · K08 CA133521-01A1 · United States
NIAID NIH HHS · R01 AI079243-01 · United States
NHLBI NIH HHS · K99HL102228 · United States
NHLBI NIH HHS · K99 HL102228 · United States
NHLBI NIH HHS · K99 HL102228-01 · United States
NIAID NIH HHS · 1R01AI079243-01 · United States
NIAID NIH HHS · R01 AI079243 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2010.06.013 PMC Full Text View journal details
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