PMID- 37489754
OWN - NLM
STAT- MEDLINE
DCOM- 20230807
LR  - 20230809
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2023 Jul 25
TI  - Two RNA-binding proteins mediate the sorting of miR223 from mitochondria into 
      exosomes.
LID - 10.7554/eLife.85878 [doi]
LID - e85878
AB  - Fusion of multivesicular bodies (MVBs) with the plasma membrane results in the 
      secretion of intraluminal vesicles (ILVs), or exosomes. The sorting of one 
      exosomal cargo RNA, miR223, is facilitated by the RNA-binding protein, YBX1 
      (Shurtleff et al., 2016). We found that miR223 specifically binds a 'cold shock' 
      domain (CSD) of YBX1 through a 5' proximal sequence motif UCAGU that may 
      represent a binding site or structural feature required for sorting. Prior to 
      sorting into exosomes, most of the cytoplasmic miR223 resides in mitochondria. An 
      RNA-binding protein localized to the mitochondrial matrix, YBAP1, appears to 
      serve as a negative regulator of miR223 enrichment into exosomes. miR223 levels 
      decreased in the mitochondria and increased in exosomes after loss of YBAP1. We 
      observed YBX1 shuttle between mitochondria and endosomes in live cells. YBX1 also 
      partitions into P body granules in the cytoplasm (Liu et al., 2021). We propose a 
      model in which miR223 and likely other miRNAs are stored in mitochondria and are 
      then mobilized by YBX1 to cytoplasmic phase condensate granules for capture into 
      invaginations in the endosome that give rise to exosomes.
CI  - (c) 2023, Ma et al.
FAU - Ma, Liang
AU  - Ma L
AUID- ORCID: 0000-0003-3227-5917
AD  - Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 
      University of California, Berkeley, United States.
FAU - Singh, Jasleen
AU  - Singh J
AD  - Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 
      University of California, Berkeley, United States.
FAU - Schekman, Randy
AU  - Schekman R
AUID- ORCID: 0000-0001-8615-6409
AD  - Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 
      University of California, Berkeley, United States.
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230725
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (MicroRNAs)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
UOF - doi: 10.1101/2023.01.11.523558
MH  - *Exosomes/metabolism
MH  - Endosomes/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Multivesicular Bodies/metabolism
MH  - Mitochondria/metabolism
MH  - RNA-Binding Proteins/genetics/metabolism
PMC - PMC10403255
OTO - NOTNLM
OT  - RNA-binding proteins
OT  - cell biology
OT  - exosome
OT  - human
OT  - mitochondria
COIS- LM, JS, RS No competing interests declared
EDAT- 2023/07/25 13:09
MHDA- 2023/08/07 06:42
PMCR- 2023/07/25
CRDT- 2023/07/25 07:53
PHST- 2022/12/30 00:00 [received]
PHST- 2023/07/24 00:00 [accepted]
PHST- 2023/08/07 06:42 [medline]
PHST- 2023/07/25 13:09 [pubmed]
PHST- 2023/07/25 07:53 [entrez]
PHST- 2023/07/25 00:00 [pmc-release]
AID - 85878 [pii]
AID - 10.7554/eLife.85878 [doi]
PST - epublish
SO  - Elife. 2023 Jul 25;12:e85878. doi: 10.7554/eLife.85878.