Subcellular mRNA Localization Regulates Ribosome Biogenesis in Migrating Cells.

Abstract:

: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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Dermit M,Dodel M,Lee FCY,Azman MS,Schwenzer H,Jones JL,Blagden SP,Ule J,Mardakheh FK

doi

10.1016/j.devcel.2020.10.006

subject

Has Abstract

pub_date

2020-11-09 00:00:00

pages

298-313.e10

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(20)30796-6

journal_volume

55

pub_type

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