N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing
2023 | journal article. A publication with affiliation to the University of Göttingen.
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N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing
Wang, C.; Ulryck, N.; Herzel, L.; Pythoud, N.; Kleiber, N.; Guérineau, V. & Jactel, V. et al. (2023)
Nucleic Acids Research, art. gkad487. DOI: https://doi.org/10.1093/nar/gkad487
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- Authors
- Wang, Can; Ulryck, Nathalie; Herzel, Lydia; Pythoud, Nicolas; Kleiber, Nicole; Guérineau, Vincent; Jactel, Vincent; Moritz, Chloé; Bohnsack, Markus T. ; Carapito, Christine; Graille, Marc
- Abstract
- Abstract Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation and translation. Dysregulation of such modifications and the enzymes installing them have been linked to various human pathologies including neurodevelopmental disorders and cancers. Several methyltransferases (MTases) are regulated allosterically by human TRMT112 (Trm112 in Saccharomyces cerevisiae), but the interactome of this regulator and targets of its interacting MTases remain incompletely characterized. Here, we have investigated the interaction network of human TRMT112 in intact cells and identify three poorly characterized putative MTases (TRMT11, THUMPD3 and THUMPD2) as direct partners. We demonstrate that these three proteins are active N2-methylguanosine (m2G) MTases and that TRMT11 and THUMPD3 methylate positions 10 and 6 of tRNAs, respectively. For THUMPD2, we discovered that it directly associates with the U6 snRNA, a core component of the catalytic spliceosome, and is required for the formation of m2G, the last ‘orphan’ modification in U6 snRNA. Furthermore, our data reveal the combined importance of TRMT11 and THUMPD3 for optimal protein synthesis and cell proliferation as well as a role for THUMPD2 in fine-tuning pre-mRNA splicing.
- Issue Date
- 2023
- Journal
- Nucleic Acids Research
- Project
- SFB 1565: Molekulare Mechanismen und Vernetzung von Prozessen der Genexpression
SFB 1565 | P12: Posttranslationale Regulation von Ribonukleasen und ihrer Funktionen in Prozessierung und Abbau unterschiedlicher Klassen von RNAs unter Zellstress
SFB 1565 | P18: Der Einfluss von RNA-Modifikationen auf die Entstehung von tRNA-Fragmenten, deren molekularen Interaktionen und diversen Funktionen in der Regulation der Genexpression
EXC 2067: Multiscale Bioimaging - Working Group
- RG K. Bohnsack (RNA Metabolism)
RG M. Bohnsack (Molecular Biology) - ISSN
- 0305-1048
- eISSN
- 1362-4962
- Language
- English