G3BP-driven RNP granules promote inhibitory RNA-RNA interactions resolved by DDX3X to regulate mRNA translatability
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
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
Originalsprache | Englisch |
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Seiten (von - bis) | 585-601.e11 |
Fachzeitschrift | Molecular cell |
Jahrgang | 85 |
Ausgabenummer | 3 |
Frühes Online-Datum | 26 Dez. 2024 |
Publikationsstatus | Veröffentlicht - 6 Feb. 2025 |
Peer-Review-Status | Ja |
Externe IDs
ORCID | /0000-0002-2213-2763/work/175741710 |
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ORCID | /0000-0002-6209-2364/work/175749197 |
ORCID | /0000-0003-4017-6505/work/175749359 |
unpaywall | 10.1016/j.molcel.2024.11.039 |
Scopus | 85216570955 |