mRNA location and translation rate determine protein targeting to dual destinations.
CASK
NET1
RNA localization
RhoA activity
cell migration
elongation rate
local translation
nuclear import
ribosome stalling
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
received:
13
10
2022
revised:
25
04
2023
accepted:
30
06
2023
pmc-release:
03
08
2024
medline:
7
8
2023
pubmed:
29
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
Numerous proteins are targeted to two or multiple subcellular destinations where they exert distinct functional consequences. The balance between such differential targeting is thought to be determined post-translationally, relying on protein sorting mechanisms. Here, we show that mRNA location and translation rate can also determine protein targeting by modulating protein binding to specific interacting partners. Peripheral localization of the NET1 mRNA and fast translation lead to higher cytosolic retention of the NET1 protein by promoting its binding to the membrane-associated scaffold protein CASK. By contrast, perinuclear mRNA location and/or slower translation rate favor nuclear targeting by promoting binding to importins. This mRNA location-dependent mechanism is modulated by physiological stimuli and profoundly impacts NET1 function in cell motility. These results reveal that the location of protein synthesis and the rate of translation elongation act in coordination as a "partner-selection" mechanism that robustly influences protein distribution and function.
Identifiants
pubmed: 37506697
pii: S1097-2765(23)00514-2
doi: 10.1016/j.molcel.2023.06.036
pmc: PMC10530421
mid: NIHMS1916248
pii:
doi:
Substances chimiques
RNA, Messenger
0
Oncogene Proteins
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2726-2738.e9Subventions
Organisme : NIGMS NIH HHS
ID : FI2 GM137845
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA BC011501
Pays : United States
Commentaires et corrections
Type : UpdateOf
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
Références
Proteomics. 2011 Dec;11(23):4468-76
pubmed: 21910249
Nat Rev Mol Cell Biol. 2021 Jul;22(7):483-504
pubmed: 33837370
EMBO Rep. 2005 May;6(5):420-5
pubmed: 15864293
Methods. 2017 Aug 15;126:112-129
pubmed: 28579404
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27423-27434
pubmed: 33060293
STAR Protoc. 2020 Nov 13;1(3):100168
pubmed: 33377062
Mol Cell. 2021 Apr 15;81(8):1830-1840.e8
pubmed: 33581075
Cell. 2020 Jul 23;182(2):404-416.e14
pubmed: 32610081
FEBS J. 2011 Nov;278(22):4252-60
pubmed: 21929725
Science. 2009 Jun 26;324(5935):1713-6
pubmed: 19556508
Sci Signal. 2013 Jul 23;6(285):rs12
pubmed: 23882122
PLoS One. 2011 Feb 23;6(2):e17108
pubmed: 21373644
Nat Struct Mol Biol. 2014 Sep;21(9):833-9
pubmed: 25150862
J Cell Sci. 2018 Feb 1;131(3):
pubmed: 29361525
Nature. 2008 May 1;453(7191):115-9
pubmed: 18451862
Nucleic Acids Res. 2021 Jun 21;49(11):6007-6026
pubmed: 33556964
Elife. 2021 Jun 24;10:
pubmed: 34165080
J Biol Chem. 2002 Apr 26;277(17):14581-8
pubmed: 11839749
Nat Rev Mol Cell Biol. 2015 Nov;16(11):651-64
pubmed: 26465719
FEBS J. 2011 Nov;278(22):4218-29
pubmed: 21929726
Mol Biol Cell. 2001 Jan;12(1):27-36
pubmed: 11160820
Mol Cell. 2022 Apr 7;82(7):1261-1277.e9
pubmed: 35305311
Annu Rev Biochem. 2018 Jun 20;87:421-449
pubmed: 29925264
FEBS J. 2011 Nov;278(22):4243-51
pubmed: 21929724
Mol Cell. 2003 Mar;11(3):577-90
pubmed: 12667443
Nat Commun. 2017 Oct 12;8(1):896
pubmed: 29026081
J Cell Sci. 2015 Mar 1;128(5):913-22
pubmed: 25588829
Nat Protoc. 2014 Aug;9(8):1931-43
pubmed: 25033209
FEBS J. 2011 Nov;278(22):4217
pubmed: 21929738
Trends Cell Biol. 2019 Oct;29(10):791-803
pubmed: 31427208
Front Cell Dev Biol. 2018 Feb 13;6:13
pubmed: 29497611
Nucleic Acids Res. 2009 Jan;37(Database issue):D93-7
pubmed: 18984615
Mol Cell Biol. 2013 Feb;33(3):622-34
pubmed: 23184663
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
RNA. 2021 Dec;27(12):1528-1544
pubmed: 34493599
Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6
pubmed: 23193283
PLoS One. 2011 Feb 24;6(2):e17380
pubmed: 21390328
Science. 2009 Feb 6;323(5915):793-7
pubmed: 19131594
FEBS J. 2011 Nov;278(22):4230-42
pubmed: 21929734
J Cell Sci. 2019 Jul 15;132(14):
pubmed: 31289196
Mol Cell. 2018 Nov 1;72(3):469-481.e7
pubmed: 30293783
Cell Rep. 2020 May 5;31(5):107610
pubmed: 32375038
Annu Rev Genet. 2020 Nov 23;54:265-285
pubmed: 32870732
Sci Rep. 2019 Jun 4;9(1):8267
pubmed: 31164708
J Cell Biol. 2015 Apr 13;209(1):163-80
pubmed: 25847537
Annu Rev Biochem. 2019 Jun 20;88:337-364
pubmed: 30508494
EMBO J. 2020 Nov 2;39(21):e104958
pubmed: 32946136
Nucleic Acids Res. 2020 Feb 20;48(3):1043-1055
pubmed: 31598688
Cell Mol Life Sci. 2016 Sep;73(18):3599-621
pubmed: 27015872
Wiley Interdiscip Rev RNA. 2022 Nov;13(6):e1721
pubmed: 35166036
Mol Cell. 2020 Aug 20;79(4):588-602.e6
pubmed: 32615089
Dev Cell. 2015 Nov 9;35(3):344-57
pubmed: 26555054