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
  • 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.
PMID: 33367824 DOI: 10.1093/nar/gkaa1226
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.