1. Academic Validation
  2. NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis

NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis

  • Nucleic Acids Res. 2021 Jan 25;49(2):1094-1113. doi: 10.1093/nar/gkaa1226.
Yoann Abel 1 2 3 Ana C F Paiva 4 5 Jonathan Bizarro 1 2 Marie-Eve Chagot 6 Paulo E Santo 4 5 Marie-Cécile Robert 1 2 3 Marc Quinternet 7 Franck Vandermoere 8 Pedro M F Sousa 4 5 Philippe Fort 9 Bruno Charpentier 6 Xavier Manival 6 Tiago M Bandeiras 4 5 Edouard Bertrand 1 2 3 Céline Verheggen 1 2 3
Affiliations

Affiliations

  • 1 IGMM, CNRS, Univ Montpellier, Montpellier, France.
  • 2 Equipe labellisée Ligue Nationale Contre le Cancer, Montpellier, France.
  • 3 IGH, CNRS, Univ Montpellier, Montpellier, France.
  • 4 iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2781-901, Portugal.
  • 5 Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, Oeiras, 2780-157, Portugal.
  • 6 Université de Lorraine, CNRS, IMoPA, F-54000 Nancy, France.
  • 7 Université de Lorraine, CNRS, INSERM, IBSLor, Biophysics and Structural Biology Core Facility, F-54000, Nancy, France.
  • 8 IGF, CNRS, INSERM, Univ Montpellier, Montpellier, France.
  • 9 CRBM, CNRS, Univ Montpellier, Montpellier, France.
Abstract

The PAQosome is a large complex composed of the HSP90/R2TP chaperone and a prefoldin-like module. It promotes the biogenesis of cellular machineries but it is unclear how it discriminates closely related client proteins. Among the main PAQosome clients are C/D snoRNPs and in particular their core protein NOP58. Using NOP58 mutants and proteomic experiments, we identify different assembly intermediates and show that C12ORF45, which we rename NOPCHAP1, acts as a bridge between NOP58 and PAQosome. NOPCHAP1 makes direct physical interactions with the CC-NOP domain of NOP58 and domain II of RUVBL1/2 AAA+ ATPases. Interestingly, NOPCHAP1 interaction with RUVBL1/2 is disrupted upon ATP binding. Moreover, while it robustly binds both yeast and human NOP58, it makes little interactions with NOP56 and PRPF31, two Other closely related CC-NOP proteins. Expression of NOP58, but not NOP56 or PRPF31, is decreased in NOPCHAP1 KO cells. We propose that NOPCHAP1 is a client-loading PAQosome cofactor that selects NOP58 to promote box C/D snoRNP assembly.

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