RT Journal Article
SR Electronic
T1 Biogenesis of RNA-containing extracellular vesicles at endoplasmic reticulum membrane contact sites
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.04.412379
DO 10.1101/2020.12.04.412379
A1 Bahnisikha Barman
A1 Jie Ping
A1 Evan Krystofiak
A1 Ryan Allen
A1 Nripesh Prasad
A1 Kasey Vickers
A1 James G. Patton
A1 Qi Liu
A1 Alissa M. Weaver
YR 2020
UL http://biorxiv.org/content/early/2020/12/05/2020.12.04.412379.abstract
AB RNA transferred via extracellular vesicles (EVs) can influence cell and tissue phenotypes; however, the biogenesis of RNA-containing EVs is poorly understood and even controversial. Here, we identify the conserved endoplasmic reticulum membrane contact site (MCS) linker protein VAP-A as a major regulator of the RNA and RNA-binding protein content of small and large EVs. We also identify a unique subpopulation of secreted small EVs that is highly enriched in RNA and regulated by VAP-A. Functional experiments revealed that VAP-A-regulated EVs are critical for the transfer of miR-100 between cells and for in vivo tumor formation. Lipid analysis of VAP-A-knockdown EVs revealed large alterations in lipids known to regulate EV biogenesis, including ceramides and cholesterol. Knockdown of VAP-A-binding ceramide and cholesterol transfer proteins CERT and ORP1L led to similar defects in biogenesis of RNA-containing EVs. We propose that lipid transfer at VAP-A-positive MCS drives biogenesis of a select RNA-containing EV population.Competing Interest StatementThe authors have declared no competing interest.