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Journal articles

The interaction between RPAP3 and TRBP reveals a possible involvement of the HSP90/R2TP chaperone complex in the regulation of miRNA activity

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 1.5Å 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.
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https://hal.univ-lorraine.fr/hal-03583324
Contributor : Mathieu Rederstorff Connect in order to contact the contributor
Submitted on : Monday, February 21, 2022 - 5:04:48 PM
Last modification on : Tuesday, May 17, 2022 - 2:20:03 PM
Long-term archiving on: : Sunday, May 22, 2022 - 7:11:34 PM

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Yoann Abel, Christophe Charron, Camille Virciglio, Valérie Bourguignon-Igel, Marc Quinternet, et al.. The interaction between RPAP3 and TRBP reveals a possible involvement of the HSP90/R2TP chaperone complex in the regulation of miRNA activity. Nucleic Acids Research, Oxford University Press, 2022, 50 (4), pp.2172-2189. ⟨10.1093/nar/gkac086⟩. ⟨hal-03583324⟩

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