G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Ribonucleoprotein (RNP) granules have been linked to translation regulation and disease, but their assembly and regulatory mechanisms are not well understood. Here, we show that the RNA-binding protein G3BP1 preferentially interacts with unfolded RNA, driving the assembly of RNP granule-like condensates that establish RNA-RNA interactions. These RNA-RNA interactions limit the mobility and translatability of sequestered mRNAs and stabilize the condensates. The DEAD-box RNA helicase DDX3X attenuates RNA-RNA interactions inside RNP granule-like condensates, rendering the condensates dynamic and enabling mRNA translation. Importantly, disease-associated and catalytically inactive DDX3X variants fail to resolve such RNA-RNA interactions. Inhibiting DDX3X in cultured cells accelerates RNP granule assembly and delays their disassembly, indicating that RNA-RNA interactions contribute to RNP granule stability in cells. Our findings reveal how RNP granules generate inhibitory RNA-RNA interactions that are modulated by DEAD-box RNA helicases to ensure RNA availability and translatability.

Details

OriginalspracheEnglisch
Seiten (von - bis)585-601.e11
FachzeitschriftMolecular cell
Jahrgang85
Ausgabenummer3
Frühes Online-Datum26 Dez. 2024
PublikationsstatusVeröffentlicht - 6 Feb. 2025
Peer-Review-StatusJa

Externe IDs

ORCID /0000-0002-2213-2763/work/175741710
ORCID /0000-0002-6209-2364/work/175749197
ORCID /0000-0003-4017-6505/work/175749359
unpaywall 10.1016/j.molcel.2024.11.039
Scopus 85216570955