| First Author | Labi V | Year | 2019 |
| Journal | Genes Dev | Volume | 33 |
| Issue | 23-24 | Pages | 1673-1687 |
| PubMed ID | 31699777 | Mgi Jnum | J:284194 |
| Mgi Id | MGI:6390938 | Doi | 10.1101/gad.330134.119 |
| Citation | Labi V, et al. (2019) Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat. Genes Dev 33(23-24):1673-1687 |
| abstractText | Knockout of the ubiquitously expressed miRNA-17 approximately 92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17 approximately 92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17 approximately 92:Bim interactions to the complex miR-17 approximately 92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17 approximately 92 seed matches. Blocking miR-17 approximately 92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17 approximately 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 approximately 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. |
