IRTG 1054 Lecture - Verena Labi

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

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 the 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 selectively prevented MYC-driven B cell transformation; 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. 

Website - Division of Developmental Immunology

Host: Elaine Wong (PhD student in Vigo Heissmeyer's lab)

Venue:

BioMedical Center (BMC), Room N 02.017,
Großhaderner Str. 9, Planegg-Martinsried

If you wish to talk to the speaker, please contact Katharina.Frank(at)med.uni-muenchen.de