A bifunctional H/ACA snoRNP mediates both pseudouridylation and rRNA scaffolding during ribosome assembly
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
- Katharina Schlick
- Timo Denk (ORCID: https://orcid.org/0000-0002-0761-3294)
- François Dragon (ORCID: https://orcid.org/0000-0002-6043-5626)
- Hafiza Hebbachi
- Jutta Hafner
- Dieter Kressler (ORCID: https://orcid.org/0000-0003-4855-3563)
- Katharina Schindlmaier (ORCID: https://orcid.org/0000-0002-6703-5123)
- Marina Kalinina (ORCID: https://orcid.org/0000-0001-6325-3054)
- Matthias Thoms (ORCID: https://orcid.org/0000-0001-8084-6097)
- Sara Šormaz
- Anthony K. Henras (ORCID: https://orcid.org/0000-0001-7785-9938)
- Y. Henry (ORCID: https://orcid.org/0000-0002-6282-3809)
- Simon Lebaron (ORCID: https://orcid.org/0000-0001-7348-2088)
- Sherif Ismail (ORCID: https://orcid.org/0000-0002-6063-1475)
- Priya Bhutada
- Brigitte Pertschy (ORCID: https://orcid.org/0000-0003-3558-0191)
- Annika Hausharter
- Hussein Hamze (ORCID: https://orcid.org/0009-0002-7737-0280)
- S Favre
- Ed Hurt
- Roland Beckmann
- Anna Forstner
- Erik Farquar
- Thomas Fröhlich
- Ismaël Alidou-D'Anjou
- Sarah Woodson
Institutions
- University of Copenhagen (DK)
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Johns Hopkins University (US)
- University of Fribourg (CH)
- University of Graz (AT)
- Université du Québec à Montréal (CA)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Heidelberg University (DE)
- BioTechMed-Graz (AT)
- Case Western Reserve University (US)
- University of Baltimore (US)
- Technical University of Munich (DE)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-03-21
- DOI
- https://doi.org/10.64898/2026.03.20.713187
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00