New publication by the Carell lab on structural and biochemical characterization of yeast Tcd enzymes installing the post-transcriptional modification ct6A in tRNA
Hirschmann J, Sonntag R, Heiss M, Wegrzyn E, Heinemeyer W, Carell T, Huber EM (2026) Structural and biochemical characterization of yeast Tcd enzymes installing the post-transcriptional modification ct6A in tRNA.Nucleic Acids Res, 54:gkag376 Link
Abstract:
Post-transcriptional modifications near the anticodon of transfer ribonucleic acids (tRNAs) ensure translation fidelity and accuracy. For instance, at position 37, the universally conserved and essential nucleoside N6-threonylcarbamoyladenosine (t6A) supports decoding of ANN triplets. In some organisms t6A is converted to cyclic t6A (ct6A), but only little is known about this ATP-dependent reaction and the corresponding threonylcarbamoyladenosine dehydratases (Tcds). We here show that yeast Tcds localize to the outer mitochondrial membrane and co-purify with tRNAs recognizing ANN codons. Depending on the number of TCD genes in the genome, the proteins form V-shaped hetero- or homodimers, of which at least one subunit binds and modifies tRNAs. The C-terminal, monomeric domain shares similarities with Cas9-endonucleases and assists tRNA recognition, while the N-terminal domain mediates dimerization and contains the active site. Structure-based mutagenesis and activity assays imply that yeast Tcds lack a catalytic cysteine and do not covalently bind their substrate as proposed for Escherichia coli TcdA.
Read the full paper here: https://doi.org/10.1093/nar/gkag376
