The dual life of disordered lysine-rich domains of snoRNPs in rRNA modification and nucleolar compaction

• Published in: Nature communications 2024-10, Vol.15 (1), p.9415-19, Article 9415
• Main Authors: Dominique, Carine, Maiga, Nana Kadidia, Méndez-Godoy, Alfonso, Pillet, Benjamin, Hamze, Hussein, Léger-Silvestre, Isabelle, Henry, Yves, Marchand, Virginie, Gomes Neto, Valdir, Dez, Christophe, Motorin, Yuri, Kressler, Dieter, Gadal, Olivier, Henras, Anthony K., Albert, Benjamin
• Format: Article
• Language: English
• Subjects: 14; 14/28; 14/35; 38; 38/15; 38/90; 45/29; 45/71; 631/337/1645/2570; 631/337/384; 631/80/386/1362; 631/80/386/2383; 82/111; Assembly; Cell Nucleolus - metabolism; Compaction; DNA-directed RNA polymerase; Electrostatic properties; Evolutionary conservation; Functional plasticity; Humanities and Social Sciences; Humans; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - genetics; Intrinsically Disordered Proteins - metabolism; Life Sciences; Lysine; Lysine - chemistry; Lysine - metabolism; Mammalian cells; multidisciplinary; Nucleoli; Protein Domains; Proteomes; Regulatory mechanisms (biology); Ribonucleic acid; Ribonucleoproteins (small nucleolar); Ribonucleoproteins, Small Nucleolar - genetics; Ribonucleoproteins, Small Nucleolar - metabolism; Ribosomes - metabolism; RNA; RNA modification; RNA polymerase; RNA Polymerase I - genetics; RNA Polymerase I - metabolism; RNA, Ribosomal - chemistry; RNA, Ribosomal - genetics; RNA, Ribosomal - metabolism; rRNA; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-53805-1

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. Here, the authors unveil the evolutionary conservation of lysine-rich IDRs of snoRNPs that mediate both efficient rRNA modification during active ribosome production and nucleolar compaction when ribosome synthesis declines and snoRNPs accumulate in latent state.