MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb.
MiR-150 is a microRNA (miRNA) specifically expressed in mature lymphocytes, but not their progenitors. A top predicted target of miR-150 is c-Myb, a transcription factor controlling multiple steps of lymphocyte development. Combining loss- and gain-of-function gene targeting approaches for miR-150 with conditional and partial ablation of c-Myb, we show that miR-150 indeed controls c-Myb expression in vivo in a dose-dependent manner over a narrow range of miRNA and c-Myb concentrations and that this dramatically affects lymphocyte development and response. Our results identify a key transcription factor as a critical target of a stage-specifically expressed miRNA in lymphocytes and suggest that this and perhaps other miRNAs have evolved to control the expression of just a few critical target proteins in particular cellular contexts.
Xiao
Changchun
C
The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
Calado
Dinis Pedro
DP
Galler
Gunther
G
Thai
To-Ha
TH
Patterson
Heide Christine
HC
Wang
Jing
J
Rajewsky
Nikolaus
N
Bender
Timothy P
TP
Rajewsky
Klaus
K
D020413:3' Untranslated Regions; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D016923:Cell Death; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018390:Gene Targeting; D017930:Genes, Reporter; D006801:Humans; D007107:Immune System / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology
D020413:3' Untranslated Regions; D035683:MicroRNAs; D020598:Proto-Oncogene Proteins c-myb