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Fibrillarin-dependent 2′-O-methylation modulates RPS28 ribosome incorporation and oncogenic translation

Fibrillarin (FBL), a core component of the C/D box small nucleolar ribonucleoprotein (snoRNP) complex, catalyzes the 2′-O-methylation (Nm) of the ribose 2′-hydroxyl moiety in ribosomal RNA (rRNA). Distinct Nm patterns contribute to ribosome heterogeneity, which is linked to selective translation of...

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Hauptverfasser: Groza, Paula (VerfasserIn) , Kumari, Kanchan (VerfasserIn) , Esteva-Socias, Margalida (VerfasserIn) , Schott, Johanna (VerfasserIn) , Bhattarai, Devi Prasad (VerfasserIn) , Sajkowska, Joanna J. (VerfasserIn) , Dasgupta, Rubin (VerfasserIn) , Peula, Carlos (VerfasserIn) , Destefanis, Eliana (VerfasserIn) , Williams, Chloe (VerfasserIn) , Marchand, Virginie (VerfasserIn) , Wikström, Pernilla (VerfasserIn) , Wiberg, Rebecca (VerfasserIn) , Campos, Ana Bosch (VerfasserIn) , Gilthorpe, Jonathan D. (VerfasserIn) , Pop, Bogdan (VerfasserIn) , Mateus, Andre (VerfasserIn) , Motorin, Yuri (VerfasserIn) , Dassi, Erik (VerfasserIn) , Petzold, Katja (VerfasserIn) , Tuorto, Francesca (VerfasserIn) , Aguilo, Francesca (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 28 February 2026
In: Cancer letters
Year: 2026, Jahrgang: 639, Pages: 1-23
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.218124
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.canlet.2025.218124
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0304383525006962
Volltext
Verfasserangaben:Paula Groza, Kanchan Kumari, Margalida Esteva-Socias, Johanna Schott, Devi Prasad Bhattarai, Joanna J. Sajkowska, Rubin Dasgupta, Carlos Peula, Eliana Destefanis, Chloe Williams, Virginie Marchand, Pernilla Wikström, Rebecca Wiberg, Ana Bosch Campos, Jonathan D. Gilthorpe, Bogdan Pop, Andre Mateus, Yuri Motorin, Erik Dassi, Katja Petzold, Francesca Tuorto, Francesca Aguilo
Beschreibung
Zusammenfassung:Fibrillarin (FBL), a core component of the C/D box small nucleolar ribonucleoprotein (snoRNP) complex, catalyzes the 2′-O-methylation (Nm) of the ribose 2′-hydroxyl moiety in ribosomal RNA (rRNA). Distinct Nm patterns contribute to ribosome heterogeneity, which is linked to selective translation of oncogenes. FBL dysregulation generates an aberrant Nm signature in triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype. This study investigated the role of FBL in TNBC via translation-driven mechanisms. Our findings show that FBL knockdown impairs oncogenic traits, triggers metabolic stress, and reduces the translation efficiency of oncogenes, such as metastasis-associated protein 1 (MTA1), interleukin-1 receptor-associated kinase 1 (IRAK1), and thymosin beta 10 (TMSB10). RiboMethSeq confirmed that the rRNA Nm sites exhibited differential sensitivity to FBL depletion. Additionally, FBL knockdown led to alterations in 18S ribosome structure confirmed by SHAPE and specifically reduced RPS28 incorporation into ribosomes. Notably, silencing RPS28 also disrupted both the oncogenic phenotype and downregulated MTA1, IRAK1, and TMSB10 expression. These findings reveal a complex interplay between FBL, rRNA Nm modifications, and RPS28 in shaping oncogenic protein pools and ribosomal composition in TNBC, offering promising insights into therapeutic approaches targeting this aggressive cancer subtype.
Beschreibung:Online verfügbar: 17. November 2025, Artikelversion: 13. Dezember 2025
Gesehen am 19.02.2026
Beschreibung:Online Resource
ISSN:1872-7980
DOI:10.1016/j.canlet.2025.218124

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