Satellite cell expansion is mediated by P-eIF2α-dependent Tacc3 translation

© 2021. Published by The Company of Biologists Ltd..

Translational control of gene expression is an important regulator of adult stem cell quiescence, activation and self-renewal. In skeletal muscle, quiescent satellite cells maintain low levels of protein synthesis, mediated in part through the phosphorylation of eIF2α (P-eIF2α). Pharmacological inhibition of the eIF2α phosphatase with the small molecule sal003 maintains P-eIF2α and permits the expansion of satellite cells ex vivo Paradoxically, P-eIF2α also increases the translation of specific mRNAs, which is mediated by P-eIF2α-dependent read-through of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2α-dependent mRNA translation enables expansion of satellite cells. Using transcriptomic and proteomic analyses, we show a number of genes associated with the assembly of the spindle pole to be upregulated at the level of protein, without corresponding change in mRNA levels, in satellite cells expanded in the presence of sal003. We show that uORFs in the 5' UTR of mRNA for the mitotic spindle stability gene Tacc3 direct P-eIF2α-dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:148

Enthalten in:

Development (Cambridge, England) - 148(2021), 2 vom: 20. Jan.

Sprache:

Englisch

Beteiligte Personen:

Fujita, Ryo [VerfasserIn]
Jamet, Solène [VerfasserIn]
Lean, Graham [VerfasserIn]
Cheng, Harry Chun Man [VerfasserIn]
Hébert, Steven [VerfasserIn]
Kleinman, Claudia L [VerfasserIn]
Crist, Colin [VerfasserIn]

Links:

Volltext

Themen:

Eukaryotic Initiation Factor-2
Fetal Proteins
Journal Article
Microtubule-Associated Proteins
Muscle stem cell
PAX7 Transcription Factor
Proteome
RNA, Messenger
Research Support, Non-U.S. Gov't
Satellite cell
Skeletal muscle regeneration
TACC3
TACC3 protein, mouse

Anmerkungen:

Date Completed 22.04.2021

Date Revised 26.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1242/dev.194480

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM318833603