A bifunctional H/ACA snoRNP mediates both pseudouridylation and rRNA scaffolding during ribosome assembly
Year: 2026
Type: preprint
Abstract: The early steps of eukaryotic large ribosomal subunit assembly remain poorly understood due to the structural flexibility of pre-60S intermediates, whose rRNA is extensively modified by small nucleolar RNPs (snoRNPs). Some snoRNPs, however, lack any modification function and instead scaffold ribosome assembly through largely unknown mechanisms. Here, we show that the H/ACA snoRNP snR37 integrates both modifying and scaffolding roles. Biochemical and structural analyses reveal a canonical H/ACA core that pseudouridylates a conserved uridine in the A site of the peptidyl transferase center, the catalytic heart of the 60S subunit. Additional RNA helices recruit non-core proteins, the Upa1-Upa2 heterodimer and Rbp95, which mediate stable snR37 association with pre-60S complexes. These proteins cooperate with the Npa1 rRNA chaperone complex to link four rRNA domains, thereby structurally organizing early pre-60S intermediates and promoting proper formation of the PTC. This dual organization establishes a paradigm for snoRNPs combining rRNA modification and scaffolding functions.
Authors: Jutta Hafner, Matthias Thoms, Hussein Hamze, Anna Forstner, Ismaël Alidou-D’Anjou, Hafiza Hebbachi, Marina Kalinina, Annika Hausharter, Sébastien Favre, Simon Lebaron, Sherif Ismail, Timo Denk, Katharina Schlick, Thomas Fröhlich, Priya Bhutada, Erik Farquar, Katharina Schindlmaier, Sara Sormaz, Ed Hurt, Dieter Kressler, Yves Henry, Sarah A. Woodson, François Dragon, Roland Beckmann, Anthony K. Henras, Brigitte Pertschy
Institutions: University of Copenhagen, University of Graz, BioTechMed-Graz, Ludwig-Maximilians-Universität München, Centre National de la Recherche Scientifique, Université Toulouse III - Paul Sabatier, Université de Toulouse, Unité de biologie Moléculaire, Cellulaire et du Développement, Centre de Biologie Intégrative de Toulouse, Université du Québec à Montréal, Center of Excellence in Research on Orphan Diseases – Fondation Courtois, Johns Hopkins University, University of Fribourg, Heidelberg University, Case Western Reserve University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Energy, Case Western Reserve University, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Austrian Science Fund, Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche, Amt der Steiermärkischen Landesregierung, National Institutes of Health, Office of Science, Natural Sciences and Engineering Research Council of Canada, National Institute of General Medical Sciences, Brookhaven National Laboratory
Awards: G1059098984, G1285306620, G1740248426, G1749632606, MRI Consortium: Development of a Damping Wiggler Beamline for X-Ray Footprinting at NSLS II, G241279073, G2836680984, The Role of the snR37 H/ACA snoRNP in Ribosome Assembly, G3262563802, G357145406, G4022805576, G4495373907, G4671393316, G4971770713, Ribosome biogenesis and nucleolar function, G5765906131, G715650138, G7463374569, Tsr4, the dedicated chaperone of ribosomal protein S2, Molecular Metabolism, G832689143, G872144517, G9000232380, Assembly Mechanisms of RNA-Protein Complexes for Genetic Control
OpenAlex ID: W7140036402
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