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

Nucleic Acids Res. 2024 Feb 28;52(4):1953-1974. doi: 10.1093/nar/gkad1202.


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.

MeSH terms

  • Humans
  • Methylation
  • RNA Helicases* / genetics
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA, Ribosomal* / genetics
  • RNA, Ribosomal* / metabolism
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism
  • Ribosomes / metabolism


  • RNA Helicases
  • RNA Precursors
  • RNA, Ribosomal
  • RNA, Small Nucleolar
  • DHX15 protein, human