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Status |
Public on Jan 30, 2024 |
Title |
GPATCH4 regulates rRNA and snRNA 2’-O-methylation in both DHX15-dependent and -independent manners [RiboMeth-seq] |
Organism |
Homo sapiens |
Experiment type |
Other
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Summary |
Strict regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specify 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 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. Global analysis of rRNA and snRNA 2’-O-methylation revealed that lack of GPATCH4 impairs methylation at various sites. We further demonstrated 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.
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Overall design |
WT and GPATCH4 KO Flp-In T-Rex HEK293 cell lines or WT Flp-In T-Rex HEK293 cells treated with non-target siRNAs or those targeting DHX15 were analysed by RiboMeth-seq.
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Contributor(s) |
Kanwal N, Krogh N, Memet I, Lemus-Diaz N, Thome C, Welp L, Mizi A, Hackert P, Papantonis A, Urlaub H, Nielsen H, Bohnsack K, Bohnsack M |
Citation(s) |
38113271 |
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Submission date |
Jun 27, 2023 |
Last update date |
Mar 20, 2024 |
Contact name |
Katherine Bohnsack |
E-mail(s) |
[email protected]
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Organization name |
University Medical Centre Göttingen
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Street address |
Humboldtallee 23
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City |
Göttingen |
ZIP/Postal code |
37073 |
Country |
Germany |
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Platforms (1) |
GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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Samples (12)
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This SubSeries is part of SuperSeries: |
GSE230433 |
GPATCH4 regulates rRNA and snRNA 2'-O-methylation in both DHX15-dependent and -independent manners |
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Relations |
BioProject |
PRJNA988073 |
Supplementary file |
Size |
Download |
File type/resource |
GSE235949_RiboMeth-seq_data.xlsx |
5.5 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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