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bioRxiv · 10.1101/2020.09.11.294488

GW182 Proteins Restrict Extracellular Vesicle Mediated Selective Export of Used miRNAs In Mammalian Cancer Cells

Bhattacharyya, S. N.·Ghosh, S.·Chakrabarty, Y.·Mukherjee, K.·Ghoshal, B.
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Abstract

MicroRNAs 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 turn over in cancer cells, we explored the effect of "usage" of specific miRNAs for translation repression of their targets on the abundance of that miRNA. We have noted an accelerated extracellular vesicle mediated export of "used" miRNAs in mammalian cells and the miRNA-export process get 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 HuR mediated auxiliary pathway of miRNA export. Our data thus support existence of a HuR independent pathway of miRNA export in human cells that can be targeted to increase cellular miRNA levels in cancer cells to induce senescence. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/294488v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1d6e30dorg.highwire.dtl.DTLVardef@d4ab06org.highwire.dtl.DTLVardef@282ad4org.highwire.dtl.DTLVardef@113ef76_HPS_FORMAT_FIGEXP M_FIG C_FIG Key PointsO_LIUsage of miRNA is proportional with its export and turnover C_LIO_LIGW182 proteins cause phase separation of Ago2 to P-bodies and restrict miRNA export via extracellular vesicles (EVs) C_LIO_LIHuR driven auxiliary path of miRNA export is independent of GW182 controlled main path of miRNA exclusion C_LI

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Bhattacharyya, S. N., Ghosh, S., Chakrabarty, Y., Mukherjee, K., Ghoshal, B.. 2020-09-12. GW182 Proteins Restrict Extracellular Vesicle Mediated Selective Export of Used miRNAs In Mammalian Cancer Cells. https://doi.org/10.1101/2020.09.11.294488

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