| Literature DB >> 35150569 |
Yoann Abel1,2,3, Christophe Charron1, Camille Virciglio1, Valérie Bourguignon-Igel1, Marc Quinternet4, Marie-Eve Chagot1, Marie-Cécile Robert5,2,3, Céline Verheggen5,2,3, Christiane Branlant1, Edouard Bertrand5,2,3, Xavier Manival1, Bruno Charpentier1, Mathieu Rederstorff1.
Abstract
MicroRNAs silence mRNAs by guiding the RISC complex. RISC assembly occurs following cleavage of pre-miRNAs by Dicer, assisted by TRBP or PACT, and the transfer of miRNAs to AGO proteins. The R2TP complex is an HSP90 co-chaperone involved in the assembly of ribonucleoprotein particles. Here, we show that the R2TP component RPAP3 binds TRBP but not PACT. The RPAP3-TPR1 domain interacts with the TRBP-dsRBD3, and the 1.5 Å resolution crystal structure of this complex identifies key residues involved in the interaction. Remarkably, binding of TRBP to RPAP3 or Dicer is mutually exclusive. Additionally, we found that AGO(1/2), TRBP and Dicer are all sensitive to HSP90 inhibition, and that TRBP sensitivity is increased in the absence of RPAP3. Finally, RPAP3 seems to impede miRNA activity, raising the possibility that the R2TP chaperone might sequester TRBP to regulate the miRNA pathway.Entities:
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Year: 2022 PMID： 35150569 PMCID： PMC8887487 DOI： 10.1093/nar/gkac086
Source DB: PubMed Journal: Nucleic Acids Res ISSN： 0305-1048 Impact factor: 16.971