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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/71982 |
| _version_ | 1811227748095492096 |
|---|---|
| author | Xiao-Man Liu Liang Ma Randy Schekman |
| author_facet | Xiao-Man Liu Liang Ma Randy Schekman |
| author_sort | Xiao-Man Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T09:46:54Z |
| format | Article |
| id | doaj.art-bbf999da97cc49788361cf2fe91973c5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:46:54Z |
| publishDate | 2021-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bbf999da97cc49788361cf2fe91973c52022-12-22T03:37:56ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.71982Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensatesXiao-Man Liu0https://orcid.org/0000-0001-9968-3988Liang Ma1Randy Schekman2https://orcid.org/0000-0001-8615-6409Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesExosomes 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.https://elifesciences.org/articles/71982phase separationexosomesmiRNAYBX1P-bodies |
| spellingShingle | Xiao-Man Liu Liang Ma Randy Schekman Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates eLife phase separation exosomes miRNA YBX1 P-bodies |
| title | 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_short | Selective sorting of microRNAs into exosomes by phase-separated YBX1 condensates |
| title_sort | selective sorting of micrornas into exosomes by phase separated ybx1 condensates |
| topic | phase separation exosomes miRNA YBX1 P-bodies |
| url | https://elifesciences.org/articles/71982 |
| work_keys_str_mv | AT xiaomanliu selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates AT liangma selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates AT randyschekman selectivesortingofmicrornasintoexosomesbyphaseseparatedybx1condensates |