KAPOSIN B-MEDIATED MECHANORESPONSIVE SIGNALLING CONTROLS PROCESSING BODY DISASSEMBLY

Abstract

Kaposin B (KapB) is a viral protein that induces the formation of actin stress fibres (SFs) and promotes stabilization of inflammatory and angiogenic mRNAs by disassembling processing bodies (PBs). PBs are ribonucleoprotein granules that control mRNA post-transcriptional expression. The canonical cytoskeletal regulatory GTPase, RhoA, is required for both KapB-mediated phenotypes – the formation of SFs and PB disassembly. I investigated signalling controlling SF formation, bundling and contractility in the mechanism of KapB-induced PB disassembly. Knockdown of RhoA-effectors known to coordinate SF formation restored PBs in KapB-expressing cells. Inhibition of actomyosin contractility also restored PBs, while inducing contraction disassembled PBs. Since SFs mediate mechanotransduction, YAP was investigated and shown to mediate PB disassembly in the context of KapB and other mechanical forces, including shear stress. Using a viral protein, my research identified and dissected a novel mechanoresponsive pathway controlling PB turnover and the concomitant stability of inflammatory and angiogenic transcripts.