GW182 Proteins Restrict Extracellular Vesicle-Mediated Export of MicroRNAs in Mammalian Cancer Cells
Abstract
MicroRNAs (miRNAs) are small regulatory RNAs of relatively long half-life in non-proliferative human cells. However, in cancer cells the half-lives of miRNAs are comparatively short. To understand the mechanism of rapid miRNA turnover in cancer cells, we explored the effect of target mRNAs on the abundance of the miRNAs that repress them. We have noted an accelerated extracellular vesicle (EV)-mediated export of miRNAs in presence of their target mRNAs in mammalian cells, and this target-driven miRNA-export process is retarded by Ago2-interacting protein GW182B. The GW182 group of proteins are localized to GW182 bodies or RNA processing bodies in mammalian cells, and GW182B-dependent retardation of miRNA export depends on GW body integrity and is independent of the HuR protein-mediated auxiliary pathway of miRNA export. Our data thus support the existence of a HuR-independent pathway of miRNA export in human cells that can be targeted in MDA-MB-231 cancer cells, to increase the level of cellular let-7a, a known negative regulator of cancer growth.
Additional Information
© 2021 American Society for Microbiology. Received September 11, 2020. Returned for modification October 24, 2020. Accepted March 4, 2021. Published online April 22, 2021. We thank W. Filipowicz, G. Meister, R. Pillai, and E. Bertrand for their generous help with reagents and plasmid constructs. We also thank B. Barman, who helped us with plasmid construction. We thank T. Muruganandan for atomic force microscopy analysis. This work was primarily funded by the Swarnajayanti Fellowship (DST/SJF/LSA-03/2014-15) and CEFIPRA (6003-2) grant to S.N.B. S.N.B. also acknowledge a High Risk High Reward grant (HRR/2016/000093) from the Department of Science and Technology, Government of India. All the authors except S.N.B. and K.M. were supported by a fellowship from CSIR. The work was conceived and analyzed by S.N.B., and he was helped by other authors in formulating, analyzing, and critical reading of the text and figures. S.G., K.M., Y.C., S.C. and B.G. did all the experiments and data analysis. K.M. and S.G. also contributed to conceptualization of the idea. We declare no conflict of interest related to this article.Attached Files
Published - Molecular_and_Cellular_Biology-2021-Ghosh-e00483-20.full.pdf
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Additional details
- PMCID
- PMC8088265
- Eprint ID
- 108884
- Resolver ID
- CaltechAUTHORS:20210429-144553614
- DST/SJF/LSA-03/2014-15
- Department of Science and Technology (India)
- 6003-2
- Indo-French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA)
- HRR/2016/000093
- Science and Engineering Research Board (SERB)
- Council of Scientific and Industrial Research (India)
- Created
-
2021-05-03Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field