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

Mukherjee, Kamalika and Ghoshal, Bartika and Ghosh, Souvik and Chakrabarty, Yogaditya and Shwetha, Shivaprasad and Das, Saumitra and Bhattacharyya, Suvendra N (2016) Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. In: EMBO REPORTS, 17 (8). pp. 1184-1203.

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Abstract

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

Item Type:	Journal Article
Publication:	EMBO REPORTS
Additional Information:	Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	28 Oct 2016 06:41
Last Modified:	28 Oct 2016 06:41
URI:	http://eprints.iisc.ac.in/id/eprint/54653

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