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HACA
Deciphering the early steps in the H/ACA RNP assembly
FunderFrench National Research Agency (ANR)
Funder Contribution €533,889.00
DurationFrom 01 Jan 2026
Project codeANR-25-CE11-1131
Identifiers
Description
This project is devoted to studying the biogenesis of the various classes of H/ACA RNPs (sno-, sca- and Telomerase). They contain one H/ACA RNA associated with two hetero-tetramers of GAR1, NHP2, NOP10, and DKC1 (Psi-synthase) proteins. H/ACA RNPs are involved in several crucial processes in cells like Psi formation in ribosomal RNAs and UsnRNAs, or telomere synthesis. H/ACA RNP biogenesis requires chaperones and co-factors to promote assembly, tertiary and quaternary folding like the R2TP, SHQ1, NAF1, and DPCD. R2TP is a generalist assembly platform that chaperones macromolecular complexes. It consists of a RPAP3:PIH1D1 hetero-dimer, associated with a hetero-hexamer of RUVBL1 and RUVBL2, which are AAA+ ATPases. The function of R2TP in the H/ACA RNP assembly is still unclear. Given the large repertoire of box H/ACA RNPs with multiple crucial functions in cells and that defects in their biogenesis are linked to multiple diseases, it is essential to understand how this assembly is catalyzed and regulated. On the basis of our preliminary data, we propose that several protein-only intermediate complexes are formed successively during the early stages of H/ACA RNP assembly before association with the H/ACA RNAs. We will address the following questions: 1) What are the protein-only pre-complexes successively formed before the interaction of the core proteins with H/ACA RNA? What are their compositions, stoichiometries, and 3D structures? 2) What is the function of the R2TP in SHQ1 recruitment/release, and the importance of its ATPase activity? 3) What are the molecular determinants of R2TP specificity towards H/ACA RNP assembly, and especially what is the function of DPCD in this process? To achieve this, we will use cutting-edge techniques: (i) in vivo IP purification of cellular macro-complexes, (ii) in vitro reconstitution of pre-complexes by co-expression, (iii) nMS and MP for their characterization, and (iv) single-particle cryo-EM for their 3D structure resolution.
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This project is devoted to studying the biogenesis of the various classes of H/ACA RNPs (sno-, sca- and Telomerase). They contain one H/ACA RNA associated with two hetero-tetramers of GAR1, NHP2, NOP10, and DKC1 (Psi-synthase) proteins. H/ACA RNPs are involved in several crucial processes in cells like Psi formation in ribosomal RNAs and UsnRNAs, or telomere synthesis. H/ACA RNP biogenesis requires chaperones and co-factors to promote assembly, tertiary and quaternary folding like the R2TP, SHQ1, NAF1, and DPCD. R2TP is a generalist assembly platform that chaperones macromolecular complexes. It consists of a RPAP3:PIH1D1 hetero-dimer, associated with a hetero-hexamer of RUVBL1 and RUVBL2, which are AAA+ ATPases. The function of R2TP in the H/ACA RNP assembly is still unclear. Given the large repertoire of box H/ACA RNPs with multiple crucial functions in cells and that defects in their biogenesis are linked to multiple diseases, it is essential to understand how this assembly is catalyzed and regulated. On the basis of our preliminary data, we propose that several protein-only intermediate complexes are formed successively during the early stages of H/ACA RNP assembly before association with the H/ACA RNAs. We will address the following questions: 1) What are the protein-only pre-complexes successively formed before the interaction of the core proteins with H/ACA RNA? What are their compositions, stoichiometries, and 3D structures? 2) What is the function of the R2TP in SHQ1 recruitment/release, and the importance of its ATPase activity? 3) What are the molecular determinants of R2TP specificity towards H/ACA RNP assembly, and especially what is the function of DPCD in this process? To achieve this, we will use cutting-edge techniques: (i) in vivo IP purification of cellular macro-complexes, (ii) in vitro reconstitution of pre-complexes by co-expression, (iii) nMS and MP for their characterization, and (iv) single-particle cryo-EM for their 3D structure resolution.
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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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