GPATCH4 regulates rRNA and snRNA 2'-O-methylation in both DHX15-dependent and DHX15-independent manners.

Autor:	Kanwal N; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany., Krogh N; Department of Cellular and Molecular Medicine, University of Copenhagen, 3B Blegdamsvej, 2200N Copenhagen, Denmark., Memet I; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany., Lemus-Diaz N; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany., Thomé CC; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany., Welp LM; Max Planck Institute for Multidisciplinary Sciences, Bioanalytical Mass Spectrometry, Am Fassberg 11, 37077 Göttingen, Germany.; Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Straße 40, 35075 Göttingen, Germany., Mizi A; Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Straße 40, 35075 Göttingen, Germany., Hackert P; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany., Papantonis A; Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Straße 40, 35075 Göttingen, Germany., Urlaub H; Max Planck Institute for Multidisciplinary Sciences, Bioanalytical Mass Spectrometry, Am Fassberg 11, 37077 Göttingen, Germany.; Institute for Clinical Chemistry, University Medical Center Göttingen, Robert-Koch-Straße 40, 35075 Göttingen, Germany.; Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.; Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Göttingen., Nielsen H; Department of Cellular and Molecular Medicine, University of Copenhagen, 3B Blegdamsvej, 2200N Copenhagen, Denmark., Bohnsack KE; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.; Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany., Bohnsack MT; Department of Molecular Biology, University Medical Center Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.; Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.; Cluster of Excellence 'Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Göttingen.; Max Planck Institute for Multidisciplinary Sciences, Am Fassberg 11, 37077 Göttingen, Germany.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Feb 28; Vol. 52 (4), pp. 1953-1974.
DOI:	10.1093/nar/gkad1202
Abstrakt:	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. (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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