Reversible HuR‐microRNA binding controls extracellular export of miR‐122 and augments stress response

• DOI: 10.15252/embr.201541930
• Publication Date: 2016-07-12T03:10:54Z
• Authors: Kamalika Mukherjee; Bartika Ghoshal; Souvik Ghosh; Yogaditya Chakrab...; Shivaprasad Shwetha; Saumitra Das; Suvendra N Bhatta...
• Keywords: 0301 basic medicine; TOR Serine-Threonine Kinases; Ubiquitination; Articles; Models, Biological; RNA Transport; ELAV-Like Protein 1; Extracellular Vesicles; MicroRNAs; 03 medical and health sciences; Stress, Physiological; Cell Line, Tumor; Argonaute Proteins; Hepatocytes; Humans; 3' Untranslated Regions; Protein Binding

microRNAs (miRNAs), the tiny but stable regulatory RNAs in metazoan cells, can undergo selective turnover presence of specific internal and external cues to control cellular response against changing environment. We have observed reduction miR-122 content, due their accelerated extracellular export human hepatic cells starved for small metabolites including amino acids. In this context, a new role ELAV protein HuR has been identified. HuR, negative regulator miRNA function, accelerates vesicle (EV)-mediated miRNAs cells. stressed replaces miRNPs from target messages is both necessary sufficient corresponding miRNAs. could reversibly bind replace them Ago2 subsequently itself gets freed bound upon ubiquitination. The ubiquitinated form predominantly associated with multivesicular bodies (MVB) where HuR-unbound also reside. These MVB-associated pool get exported out via EVs thereby delimiting level during starvation. Therefore, by modulating miR-122, stress