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Abstract
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.