The conserved Wobble uridine tRNA thiolase Ctu1–Ctu2 is required to maintain genome integrity
- 8 April 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (14), 5459-5464
- https://doi.org/10.1073/pnas.0709404105
Abstract
Modified nucleosides close to the anticodon are important for the proper decoding of mRNA by the ribosome. Particularly, the uridine at the first anticodon position (U34) of glutamate, lysine, and glutamine tRNAs is universally thiolated (S(2)U34), which is proposed to be crucial for both restriction of wobble in the corresponding split codon box and efficient codon-anticodon interaction. Here we show that the highly conserved complex Ctu1-Ctu2 (cytosolic thiouridylase) is responsible for the 2-thiolation of cytosolic tRNAs in the nematode and fission yeast. In both species, inactivation of the complex leads to loss of thiolation on tRNAs and to a thermosensitive decrease of viability associated with marked ploidy abnormalities and aberrant development. Increased level of the corresponding tRNAs suppresses the fission yeast defects, and our data suggest that these defects could result from both misreading and frame shifting during translation. Thus, a translation defect due to unmodified tRNAs results in severe genome instability.Keywords
This publication has 50 references indexed in Scilit:
- Trm9-Catalyzed tRNA Modifications Link Translation to the DNA Damage ResponseMolecular Cell, 2007
- A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeastRNA, 2007
- Human cancers express a mutator phenotypeProceedings of the National Academy of Sciences, 2006
- tRNA’s Wobble Decoding of the Genome: 40 Years of ModificationJournal of Molecular Biology, 2006
- The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative RNomics, decoding strategies, transcription and evolutionary implicationsNucleic Acids Research, 2006
- Dual function of the tRNA(m5U54)methyltransferase in tRNA maturationRNA, 2002
- Improvement of reading frame maintenance is a common function for several tRNA modificationsThe EMBO Journal, 2001
- TATA box mutations in the Schizosaccharomyces pombe nmt1 promoter affect transcription efficiency but not the transcription start point or thiamine repressibilityGene, 1993
- Thiamine-repressible expression vectors pREP and pRIP for fission yeastGene, 1993
- [56] Molecular genetic analysis of fission yeast Schizosaccharomyces pombeMethods in enzymology, 1991