Abstract
MicroRNAs, the tiny regulators of gene expression, can be transferred between neighbouring cells via Extracellular Vesicles (EV) to control the expression of genes in both donor and recipient cells. How the EV-derived miRNAs get internalized and become functional in target cells is an unresolved question. We have expressed liver specific microRNA, miR-122, in non-hepatic cells for packaging in the released EVs. With these EVs, we have followed the trafficking of miR-122 to recipient HeLa cells that otherwise don't express this miRNA. We found that EV-associated miR-122 are primarily single stranded and, to become functional, get loaded onto the recipient cell Ago proteins without requiring host Dicer1. Following endocytosis, EV-associated miR-122 get loaded onto the host cell Ago on the endosomal membrane where the release of internalized miRNAs occurs in a pH-dependent manner facilitating the formation of the exogenous miRNP pool in the recipient cells. Endosome maturation defect affects EV-mediated entry of exogeneous miRNAs in mammalian cells.
- Received September 3, 2020.
- Accepted March 19, 2021.
- © 2021. Published by The Company of Biologists Ltd
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