Nucleic Acids Research has published our story about tRNAs
published 2026-04-20
Our new paper, published in Nucleic Acids Research as a large collaboration led by Anzhelika Butenko and Julius Lukeš (Biology Centre CAS), reveals that transfer RNAs with a shortened, 4-base-pair anticodon stem are surprisingly common across bacteria. By surveying over 42,000 bacterial genomes, the team found that these structurally unusual tRNAs are present in diverse bacterial lineages, including a newly identified case of stop-to-tryptophan UGA codon reassignment in the phylum Patescibacteriota. In some organisms, the 4-bp anticodon stem tRNA-Trp is the only form available, suggesting it plays a direct role in reading the UGA codon as tryptophan rather than as a stop signal. This was experimentally confirmed by introducing an engineered 4-bp anticodon stem tRNA-Trp into E. coli, where it enabled UGA readthrough.
Our contribution, carried out by Jakub Žváček and Michal Kolář, focused on understanding the structural mechanism behind this phenomenon using all-atom MD simulations. We simulated the wild-type E. coli tRNA-Trp alongside several variants with an unpinned top base pair in the anticodon stem. The simulations showed that disrupting this single base pair does not destabilize the tRNA globally but instead subtly and non-locally modulates its structure and dynamics. These changes likely alter how the tRNA interacts with the ribosome and enable the otherwise disfavored C:A base pairing at the wobble position.
Fakih et al. "Frequent occurrence and predicted functions of tRNAs with 4-base-pair anticodon stems in bacteria: extended superwobble hypothesis Nucl. Acids Res.
At our side, funded by Czech Science Foundation 23-05764S