The dual life of disordered lysine-rich domains of snoRNPs in rRNA modification and nucleolar compaction
Intrinsically disordered regions (IDRs) are highly enriched in the nucleolar proteome but their physiological role in ribosome assembly remains poorly understood. Our study reveals the functional plasticity of the extremely abundant lysine-rich IDRs of small nucleolar ribonucleoprotein particles (snoRNPs) from protists to mammalian cells. We show in Saccharomyces cerevisiae that the electrostatic properties of this lysine-rich IDR, the KKE/D domain, promote snoRNP accumulation in the vicinity of nascent rRNAs, facilitating their modification. Under stress conditions reducing the rate of ribosome assembly, they are essential for nucleolar compaction and sequestration of key early-acting ribosome biogenesis factors, including RNA polymerase I, owing to their self-interaction capacity in a latent, non-rRNA-associated state. We propose that such functional plasticity of these lysine-rich IDRs may represent an ancestral eukaryotic regulatory mechanism, explaining how nucleolar morphology is continuously adapted to rRNA production levels.
Authors
- Benjamin Albert (ORCID: https://orcid.org/0000-0003-2122-6458)
- Dieter Kressler (ORCID: https://orcid.org/0000-0003-4855-3563)
- Christophe Dez (ORCID: https://orcid.org/0000-0002-8526-3541)
- Anthony K. Henras (ORCID: https://orcid.org/0000-0001-7785-9938)
- Virginie Marchand (ORCID: https://orcid.org/0000-0002-8537-1139)
- Valdir Gomes Neto (ORCID: https://orcid.org/0000-0002-9412-4930)
- Carine Dominique
- Alfonso Méndez-Godoy (ORCID: https://orcid.org/0009-0009-4200-0854)
- Isabelle Léger‐Silvestre (ORCID: https://orcid.org/0000-0002-7030-5593)
- Benjamin Pillet (ORCID: https://orcid.org/0000-0002-7313-4304)
- Olivier Gadal (ORCID: https://orcid.org/0000-0001-9421-0831)
- Yuri Motorin (ORCID: https://orcid.org/0000-0002-8018-334X)
- Hussein Hamze (ORCID: https://orcid.org/0009-0002-7737-0280)
- Yves Henry (ORCID: https://orcid.org/0000-0003-2704-3169)
- Nana Kadidia Maiga
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- University of Fribourg (CH)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Universidade de São Paulo (BR)
- Universidade Cidade de São Paulo (BR)
- Ingénierie Moléculaire et Physiopathologie Articulaire (FR)
- Université de Lorraine (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1038/s41467-024-53805-1
- Citations
- 13
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- National Science Foundation
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Ministry of Economy, Trade and Industry
- Fondation ARC pour la Recherche sur le Cancer