• Codon reengineering studies suggest that Trm9-catalyzed tRNA modifications promote fidelity during the translation of specific genes, those rich in arginine and glutamic acid codons from mixed boxes. (nih.gov)
  • Together, these results suggest that Trm9-catalyzed tRNA modifications play a significant role in regulating protein expression within the cell. (genesilico.pl)
  • We hypothesized that wobble uridine modifications catalyzed by tRNA methyltransferase 9 (Trm9) are essential for translational fidelity. (nih.gov)
  • In support, we have used phenotypic, reporter and protein-based assays to demonstrate increased translational infidelity in trm9Δ Saccharomyces cerevisiae cells. (nih.gov)
  • These data support a model in which Trm9-catalyzed tRNA modifications promote fidelity during the translation of specific transcripts, with decreased wobble base modification leading to translational infidelity, protein errors and activation of protein stress response pathways. (nih.gov)
  • Controlling for bias in protein expression and alternations in mRNA expression, we find that loss of Trm9 selectively impairs expression of proteins from genes enriched with AGA and GAA codons under both normal and stress conditions. (genesilico.pl)
  • Here we use quantitative proteomics to show a direct link between wobble uridine 5-methoxycarbonylmethyl (mcm5) and 5-methoxy-carbonyl-methyl-2-thio (mcm5s2) modifications catalyzed by tRNA methyltransferase 9 (Trm9) in tRNAArg(UCU) and tRNAGlu(UUC) and selective translation of proteins from genes enriched with their cognate codons. (genesilico.pl)
  • Post-transcriptional modifications of transfer RNAs (tRNAs) have long been recognized to play crucial roles in regulating the rate and fidelity of translation. (genesilico.pl)
  • This enzyme catalyses the following chemical reaction S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA ⇌ {\displaystyle \rightleftharpoons } S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA The enzyme catalyses the posttranslational modification of uridine residues at the wobble position 34 of the anticodon loop of tRNA. (wikipedia.org)
  • Post-transcriptional modifications of anticodon loop (ACL) nucleotides impact tRNA structure, affinity for the ribosome, and decoding activity, and these activities can be fine-tuned by interactions between nucleobases on either side of the anticodon. (nih.gov)
  • TRNA (carboxymethyluridine34-5-O)-methyltransferase (EC 2.1.1.229, ALKBH8, ABH8, Trm9, tRNA methyltransferase 9) is an enzyme with systematic name S-adenosyl-L-methionine:tRNA (carboxymethyluridine34-5-O)-methyltransferase. (wikipedia.org)
  • ALKBH8 is one of two metazoan homologs of the yeast tRNA methyltransferase TRM9. (nih.gov)
  • My preliminary data suggest ALKBH8 attenuates synaptic growth by limiting oxidative stress through the methylation of tRNA- selenocysteine, which yields the rare 21st amino acid selenocysteine for the synthesis of selenoproteins. (nih.gov)
  • A recently discovered ACL modification circuit involving positions 32, 34, and 37 is disrupted by a human disease-associated mutation to the gene encoding a tRNA modification enzyme. (nih.gov)
  • The proposed experimental plan will provide mechanistic insight into how tRNA modifications regulate gene expression during nervous system development. (nih.gov)
  • tRNAs are heavily post-transcriptionally modified to regulate their structure, stability, and fidelity. (nih.gov)