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

Mukherjee, Kamalika, Ghoshal, Bartika, Ghosh, Souvik, Chakrabarty, Yogaditya, Shwetha, Shivaprasad, Das, Saumitra, Bhattacharyya, Suvendra N·2016·The EMBO Reports
DOI 10.15252/embr.201541930PMC PMC4967961
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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.

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Metadata

Authors
Mukherjee, K., Ghoshal, B., Ghosh, S., Chakrabarty, Y., Shwetha, S., Das, S., & Bhattacharyya, S. N.
ORCID
Bhattacharyya, Suvendra N
Venue
The EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2016-07-11
Volume
17
Issue
8
Pages
1184-1203
ISSN
  • 1469-221X
  • 1469-3178
DOI
10.15252/embr.201541930
PMC
PMC4967961
Cited by
184
References
3
Language
en
Licence
Funders
  • HFSPO Career Development Fund (CDA‐25/2007‐C)
  • Wellcome Trust (084324/Z/07/A)
  • Lady Tata Memorial Trust (YRA‐2009)

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