In:
Genes & Development, Cold Spring Harbor Laboratory, Vol. 33, No. 23-24 ( 2019-12-01), p. 1673-1687
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.
Type of Medium:
Online Resource
ISSN:
0890-9369
,
1549-5477
DOI:
10.1101/gad.330134.119
Language:
English
Publisher:
Cold Spring Harbor Laboratory
Publication Date:
2019
detail.hit.zdb_id:
1467414-2
SSG:
12
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