Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat.
Genes Dev
; 33(23-24): 1673-1687, 2019 12 01.
Article
in En
| MEDLINE
| ID: mdl-31699777
ABSTRACT
Knockout of the ubiquitously expressed miRNA-17â¼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17â¼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17â¼92Bim interactions to the complex miR-17â¼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17â¼92 seed matches. Blocking miR-17â¼92Bim interactions early in development phenocopied the lethal lung phenotype of miR-17â¼92 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-17â¼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Cell Survival
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Gene Expression Regulation, Developmental
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MicroRNAs
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Bcl-2-Like Protein 11
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Hematopoiesis
Limits:
Animals
Language:
En
Journal:
Genes Dev
Year:
2019
Document type:
Article