Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates

Exosomes may mediate cell-to-cell communication by transporting various proteins and nucleic acids to neighboring cells. Some protein and RNA cargoes are significantly enriched in exosomes. How cells efficiently and selectively sort them into exosomes remains incompletely explored. Previously, we re...

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Autores principales:	Xiao-Man Liu, Liang Ma, Randy Schekman
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	phase separation exosomes miRNA YBX1 P-bodies Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bbf999da97cc49788361cf2fe91973c5
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spelling	oai:doaj.org-article:bbf999da97cc49788361cf2fe91973c52021-11-24T12:43:20ZSelective sorting of microRNAs into exosomes by phase-separated YBX1 condensates10.7554/eLife.719822050-084Xe71982https://doaj.org/article/bbf999da97cc49788361cf2fe91973c52021-11-01T00:00:00Zhttps://elifesciences.org/articles/71982https://doaj.org/toc/2050-084XExosomes may mediate cell-to-cell communication by transporting various proteins and nucleic acids to neighboring cells. Some protein and RNA cargoes are significantly enriched in exosomes. How cells efficiently and selectively sort them into exosomes remains incompletely explored. Previously, we reported that YBX1 is required in sorting of miR-223 into exosomes. Here, we show that YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells. YBX1 condensates selectively recruit miR-223 in vitro and into exosomes secreted by cultured cells. Point mutations that inhibit YBX1 phase separation impair the incorporation of YBX1 protein into biomolecular condensates formed in cells, and perturb miR-233 sorting into exosomes. We propose that phase separation-mediated local enrichment of cytosolic RNA-binding proteins and their cognate RNAs enables their targeting and packaging by vesicles that bud into multivesicular bodies. This provides a possible mechanism for efficient and selective engulfment of cytosolic proteins and RNAs into intraluminal vesicles which are then secreted as exosomes from cells.Xiao-Man LiuLiang MaRandy SchekmaneLife Sciences Publications Ltdarticlephase separationexosomesmiRNAYBX1P-bodiesMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	phase separation exosomes miRNA YBX1 P-bodies Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	phase separation exosomes miRNA YBX1 P-bodies Medicine R Science Q Biology (General) QH301-705.5 Xiao-Man Liu Liang Ma Randy Schekman Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
description	Exosomes may mediate cell-to-cell communication by transporting various proteins and nucleic acids to neighboring cells. Some protein and RNA cargoes are significantly enriched in exosomes. How cells efficiently and selectively sort them into exosomes remains incompletely explored. Previously, we reported that YBX1 is required in sorting of miR-223 into exosomes. Here, we show that YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells. YBX1 condensates selectively recruit miR-223 in vitro and into exosomes secreted by cultured cells. Point mutations that inhibit YBX1 phase separation impair the incorporation of YBX1 protein into biomolecular condensates formed in cells, and perturb miR-233 sorting into exosomes. We propose that phase separation-mediated local enrichment of cytosolic RNA-binding proteins and their cognate RNAs enables their targeting and packaging by vesicles that bud into multivesicular bodies. This provides a possible mechanism for efficient and selective engulfment of cytosolic proteins and RNAs into intraluminal vesicles which are then secreted as exosomes from cells.
format	article
author	Xiao-Man Liu Liang Ma Randy Schekman
author_facet	Xiao-Man Liu Liang Ma Randy Schekman
author_sort	Xiao-Man Liu
title	Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
title_short	Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
title_full	Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
title_fullStr	Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
title_full_unstemmed	Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates
title_sort	selective sorting of micrornas into exosomes by phase-separated ybx1 condensates
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/bbf999da97cc49788361cf2fe91973c5
work_keys_str_mv	AT xiaomanliu selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates AT liangma selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates AT randyschekman selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates
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Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates

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