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Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat

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Item Type:Article
Title:Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat
Creators Name:Labi, V. and Peng, S. and Klironomos, F. and Munschauer, M. and Kastelic, N. and Chakraborty, T. and Schoeler, K. and Derudder, E. and Martella, M. and Mastrobuoni, G. and Hernandez-Miranda, L.R. and Lahmann, I. and Kocks, C. and Birchmeier, C. and Kempa, S. and Quintanilla-Martinez de Fend, L. and Landthaler, M. and Rajewsky, N. and Rajewsky, K.
Abstract:Knockout of the ubiquitously expressed miRNA-17~92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17~92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17~92:Bim interactions to the complex miR-17~92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17~92 seed matches. Blocking miR-17~92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17~92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17~92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.
Keywords:Apoptosis, BIM, miR-17∼92, Seed Match Mutation, B Cells, Lung Development, Animals, Mice
Source:Genes & Development
Publisher:Cold Spring Harbor Laboratory Press
Page Range:23-24
Date:7 November 2019
Official Publication:https://doi.org/10.1101/gad.330134.119
PubMed:View item in PubMed

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