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  3. A bifunctional H/ACA snoRNP mediates both pseudouridylation and rRNA scaffolding during ribosome assembly

A bifunctional H/ACA snoRNP mediates both pseudouridylation and rRNA scaffolding during ribosome assembly

  • bioRxiv. 2026 Apr 1:2026.03.20.713187. doi: 10.64898/2026.03.20.713187.
Jutta Hafner 1 2 3 4,  Matthias Thoms 5 4,  Hussein Hamze 6,  Anna Forstner 1 3,  Ismaël Alidou-D'Anjou 7 8,  Hafiza Hebbachi 7,  Marina Kalinina 9,  Annika Hausharter 1 3,  Sébastien Favre 10,  Simon Lebaron 6,  Sherif Ismail 11,  Timo Denk 5,  Katharina Schlick 1,  Thomas Fröhlich 5,  Priya Bhutada 1,  Erik Farquar 12,  Katharina Schindlmaier 1 3,  Sara Sormaz 1 3,  Ed Hurt 11,  Dieter Kressler 10,  Yves Henry 6,  Sarah A Woodson 9,  François Dragon 7 8,  Roland Beckmann 5,  Anthony K Henras 6,  Brigitte Pertschy 1 3 13
Affiliations

Affiliations

  • 1 Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50, 8010 Graz, Austria.
  • 2 Present address: Biotech Research and Innovation Center, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
  • 3 BioTechMed-Graz, Graz, Austria.
  • 4 These authors contributed equally.
  • 5 Gene Center, University of Munich, Feodor-Lynen-Straße 25, 81377 Munich, Germany.
  • 6 Molecular, Cellular and Developmental Biology Unit (MCD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062, Toulouse, France.
  • 7 Département des sciences biologiques, Université du Québec à Montréal, 141 Av. du Président-Kennedy, Montréal, QC, H2X 1Y4, Canada.
  • 8 Centre d'excellence en recherche sur les maladies orphelines - Fondation Courtois (CERMO-FC), Université du Québec à Montréal, 141 Av. du Président-Kennedy, Montréal, QC, H2X 1Y4, Canada.
  • 9 T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 N. Charles St., Baltimore, MD 21218, United States.
  • 10 Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
  • 11 Biochemistry Center, University of Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
  • 12 Center for Synchrotron Biosciences, Case Western University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
  • 13 Lead contact.
PMID: 41889967 DOI: 10.64898/2026.03.20.713187
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.

Keywords

H/ACA snoRNP; Npa1 complex; RNA folding; ribosome biogenesis; snR37; snoRNA; yeast.

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