Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.
Autoantigens
/ metabolism
Cell Movement
Cell Proliferation
Cell Surface Extensions
/ metabolism
Epithelial-Mesenchymal Transition
Humans
Neoplasms
/ metabolism
Organelle Biogenesis
Protein Binding
Protein Biosynthesis
RNA Transport
RNA, Messenger
/ genetics
Ribonucleoproteins
/ metabolism
Ribosomal Proteins
/ metabolism
Ribosomes
/ metabolism
Subcellular Fractions
/ metabolism
Transcriptome
/ genetics
SS-B Antigen
EMT
LARP6
La-related proteins
RNA localization
cancer
invasion
protrusion
ribosomal proteins
ribosome biogenesis
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
09 11 2020
09 11 2020
Historique:
received:
16
01
2020
revised:
01
09
2020
accepted:
08
10
2020
entrez:
10
11
2020
pubmed:
11
11
2020
medline:
12
3
2021
Statut:
ppublish
Résumé
Translation of ribosomal protein-coding mRNAs (RP-mRNAs) constitutes a key step in ribosome biogenesis, but the mechanisms that modulate RP-mRNA translation in coordination with other cellular processes are poorly defined. Here, we show that subcellular localization of RP-mRNAs acts as a key regulator of their translation during cell migration. As cells migrate into their surroundings, RP-mRNAs localize to the actin-rich cell protrusions. This localization is mediated by La-related protein 6 (LARP6), an RNA-binding protein that is enriched in protrusions. Protrusions act as hotspots of translation for RP-mRNAs, enhancing RP synthesis, ribosome biogenesis, and the overall protein synthesis in migratory cells. In human breast carcinomas, epithelial-to-mesenchymal transition (EMT) upregulates LARP6 expression to enhance protein synthesis and support invasive growth. Our findings reveal LARP6-mediated mRNA localization as a key regulator of ribosome biogenesis during cell migration and demonstrate a role for this process in cancer progression downstream of EMT.
Identifiants
pubmed: 33171110
pii: S1534-5807(20)30796-6
doi: 10.1016/j.devcel.2020.10.006
pmc: PMC7660134
pii:
doi:
Substances chimiques
Autoantigens
0
RNA, Messenger
0
Ribonucleoproteins
0
Ribosomal Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
298-313.e10Subventions
Organisme : European Research Council
ID : 617837
Pays : International
Organisme : Medical Research Council
ID : MR/P009417/1
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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