期刊
JOURNAL OF CELL SCIENCE
卷 134, 期 9, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.253914
关键词
miRNA; Extracellular vesicles; Argonaute; miRNA loading; miRNA endocytosis; Endosomes; Dicer1
类别
资金
- Swarnajayanti Fellowship from the Department of Science and Technology, Ministry of Science and Technology, India [DST/SJF/LSA-03/2014-15]
- Council of Scientific and Industrial Research, India
- Indo-French Centre for the Promotion of Advanced Research (CEFIPRA) Raman-Charpak travel exchange fellowship
- High Risk High Reward Grant from the Science and Engineering Research Board (SERB), Department of Science and Technology, Ministry of Science and Technology, Govt. of India, India [HRR/2016/00093]
- CEFIPRA project grant [6003-J]
This study demonstrates that EV-delivered miR-122 is primarily single-stranded and is loaded onto recipient cell argonaute proteins to become functional. Following endocytosis, EV-associated miR-122 is released on the endosomal membrane in a pH-dependent manner, facilitating the formation of the exogenous miRNP pool in recipient cells.
MicroRNAs (miRNAs), the tiny regulators of gene expression, can be transferred between neighbouring cells via extracellular vesicles (EVs) to control the expression of genes in both donor and recipient cells. How the EV-derived miRNAs are internalized and become functional in target cells is an unresolved question. We have expressed a liver-specific miRNA, miR-122, in non-hepatic cells for packaging in released EVs. With these EVs, we have followed the trafficking of miR-122 to recipient HeLa cells that otherwise do not express this miRNA. We found that EV-associated miR-122 is primarily single-stranded and, to become functional, is loaded onto the recipient cell argonaute proteins without requiring host Dicerl. Following endocytosis, EV-associated miR-122 is loaded onto the host cell argonaute proteins 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 defects affect EV-mediated entry of exogeneous miRNAs in mammalian cells. This article has an associated First Person interview with the first author of the paper.
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