A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis
Modified tRNA anticodons are critical for proper mRNA translation during protein synthesis. It is generally thought that almost all bacterial tRNAs<sup>Ile</sup> use a modified cytidine-lysidine (L)-at the first position (34) of the anticodon to decipher the AUA codon as isoleucine (Ile). Here we report that tRNAs<sup>Ile</sup> from plant organelles and a subset of bacteria contain a new cytidine derivative, designated 2-aminovaleramididine (ava<sup>2</sup>C). Like L34, ava<sup>2</sup>C34 governs both Ile-charging ability and AUA decoding. Cryo-electron microscopy structural analyses revealed molecular details of codon recognition by ava<sup>2</sup>C34 with a specific interaction between its terminal amide group and an mRNA residue 3'-adjacent to the AUA codon. These findings reveal the evolutionary variation of an essential tRNA modification and demonstrate the molecular basis of AUA decoding mediated by a unique tRNA modification.
Authors
- Tsutomu Suzuki (ORCID: https://orcid.org/0000-0002-9731-1731)
- Akiko Soma
- Mikako Shirouzu (ORCID: https://orcid.org/0000-0002-7997-2149)
- Akimitsu Okamoto (ORCID: https://orcid.org/0000-0002-7418-6237)
- Kazuki Inoue (ORCID: https://orcid.org/0009-0001-8245-2443)
- Kenta Koyama
- Asuteka Nagao (ORCID: https://orcid.org/0000-0002-9152-1527)
- Satoshi Kimura (ORCID: https://orcid.org/0000-0003-3555-5877)
- Kenjyo Miyauchi (ORCID: https://orcid.org/0000-0002-4075-7660)
- Gosuke Hayashi (ORCID: https://orcid.org/0000-0001-6853-2706)
- Kensuke Ishiguro (ORCID: https://orcid.org/0000-0001-6651-1960)
- Matthew K. Waldor (ORCID: https://orcid.org/0000-0003-1843-7000)
- Veerasak Srisuknimit (ORCID: https://orcid.org/0000-0002-0130-153X)
- Naho Akiyama (ORCID: https://orcid.org/0000-0002-4790-7203)
- T K Vu
Institutions
- Brigham and Women's Hospital (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Chulalongkorn University (TH)
- Chiba University (JP)
- Cornell University (US)
- RIKEN Center for Biosystems Dynamics Research (JP)
- Nagoya University (JP)
- The University of Tokyo (JP)
Publication Details
- Journal
- Nature Chemical Biology
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1038/s41589-024-01726-x
- Citations
- 20
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- Massachusetts Institute of Technology
- Japan Agency for Medical Research and Development
- Shizuoka University
- National Institutes of Health
- Japan Society for the Promotion of Science
- RIKEN
- Exploratory Research for Advanced Technology