GPATCH4 regulates rRNA and snRNA 2′- O -methylation in both DHX15-dependent and DHX15-independent manners
2023 | journal article. A publication with affiliation to the University of Göttingen.
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GPATCH4 regulates rRNA and snRNA 2′- O -methylation in both DHX15-dependent and DHX15-independent manners
Kanwal, N.; Krogh, N.; Memet, I.; Lemus-Diaz, N.; Thomé, C.; Welp, L. & Mizi, A. et al. (2023)
Nucleic Acids Research, art. gkad1202. DOI: https://doi.org/10.1093/nar/gkad1202
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Details
- Authors
- Kanwal, Nidhi; Krogh, Nicolai; Memet, Indira; Lemus-Diaz, Nicolas; Thomé, Chairini C.; Welp, Luisa M.; Mizi, Athanasia; Hackert, Philipp; Papantonis, Argyris; Urlaub, Henning; Bohnsack, Markus T.
- Abstract
- Abstract Regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specificity within the complex cellular environment. The largest family of RNA helicase cofactors are the G-patch proteins, but the cognate RNA helicases and cellular functions of numerous human G-patch proteins remain elusive. Here, we discover that GPATCH4 is a stimulatory cofactor of DHX15 that interacts with the DEAH box helicase in the nucleolus via residues in its G-patch domain. We reveal that GPATCH4 associates with pre-ribosomal particles, and crosslinks to the transcribed ribosomal DNA locus and precursor ribosomal RNAs as well as binding to small nucleolar- and small Cajal body-associated RNAs that guide rRNA and snRNA modifications. Loss of GPATCH4 impairs 2′-O-methylation at various rRNA and snRNA sites leading to decreased protein synthesis and cell growth. We demonstrate that the regulation of 2′-O-methylation by GPATCH4 is both dependent on, and independent of, its interaction with DHX15. Intriguingly, the ATPase activity of DHX15 is necessary for efficient methylation of DHX15-dependent sites, suggesting a function of DHX15 in regulating snoRNA-guided 2′-O-methylation of rRNA that requires activation by GPATCH4. Overall, our findings extend knowledge on RNA helicase regulation by G-patch proteins and also provide important new insights into the mechanisms regulating installation of rRNA and snRNA modifications, which are essential for ribosome function and pre-mRNA splicing.
- Issue Date
- 2023
- Journal
- Nucleic Acids Research
- Project
- SFB 1565: Molekulare Mechanismen und Vernetzung von Prozessen der Genexpression
SFB 1565 | P03: Multifunktionale Chromatinfaktoren bei der Kontrolle der Genexpression und Zellkernarchitektur
SFB 1565 | P04: Analyse von Protein-RNA- und -DNA-Wechselwirkungen in Zellen durch Quervernetzungs-Massenspektrometrie
SFB 1565 | P06: Die Regulation nucleoplasmatischer Schritte in Genexpressionsprozessen durch die multifunktionelle RNA-Helikase DHX15 und ihre Kofaktoren
SFB 1565 | P12: Posttranslationale Regulation von Ribonukleasen und ihrer Funktionen in Prozessierung und Abbau unterschiedlicher Klassen von RNAs unter Zellstress
EXC 2067: Multiscale Bioimaging - Working Group
- RG K. Bohnsack (RNA Metabolism)
RG M. Bohnsack (Molecular Biology)
RG Papantonis (Translational Epigenetics Laboratory)
RG Urlaub (Bioanalytik) - ISSN
- 0305-1048
- eISSN
- 1362-4962
- Language
- English
- Sponsor
- Open-Access-Publikationsfonds 2023