MiR-150 Controls B Cell Differentiation by Targeting the Transcription Factor c-Myb

• Published in: Cell Vol. 131; no. 1; pp. 146 - 159
• Main Authors: Xiao, Changchun, Calado, Dinis Pedro, Galler, Gunther, Thai, To-Ha, Patterson, Heide Christine, Wang, Jing, Rajewsky, Nikolaus, Bender, Timothy P., Rajewsky, Klaus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.10.2007
• Subjects: 3' Untranslated Regions; Animals; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Cell Death; Cell Differentiation - physiology; Cells, Cultured; Gene Expression Regulation; Gene Targeting; Genes, Reporter; Humans; Immune System - physiology; Mice; Mice, Knockout; MicroRNAs - genetics; MicroRNAs - metabolism; MOLIMMUNO; Proto-Oncogene Proteins c-myb - genetics; Proto-Oncogene Proteins c-myb - metabolism; RNA; T-Lymphocytes - physiology; RNA; MOLIMMUNO
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2007.07.021

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.