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| Item Type: | Article |
|---|---|
| Title: | Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat |
| Creators Name: | Labi, V., Peng, S., Klironomos, F., Munschauer, M., Kastelic, N., Chakraborty, T., Schoeler, K., Derudder, E., Martella, M., Mastrobuoni, G., Hernandez-Miranda, L.R., Lahmann, I., Kocks, C., Birchmeier, C., Kempa, S., Quintanilla-Martinez de Fend, L., Landthaler, M., 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 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Volume: | 33 |
| 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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