A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis

Kenjyo Miyauchi; Satoshi Kimura; Naho Akiyama; Kazuki Inoue; Kensuke Ishiguro; Thien-Son Vu; Veerasak Srisuknimit; Kenta Koyama; Gosuke Hayashi; Akiko Soma; Asuteka Nagao; Mikako Shirouzu; Akimitsu Okamoto; Matthew K Waldor; Tsutomu Suzuki

doi:10.1038/s41589-024-01726-x

A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis

Nat Chem Biol. 2024 Sep 19. doi: 10.1038/s41589-024-01726-x. Online ahead of print.

Authors

Kenjyo Miyauchi^#¹, Satoshi Kimura^#^{2

3

4

5}, Naho Akiyama^#^{1

6}, Kazuki Inoue¹, Kensuke Ishiguro^{1

6}, Thien-Son Vu¹, Veerasak Srisuknimit^{2

3

7}, Kenta Koyama¹, Gosuke Hayashi^{1

8}, Akiko Soma⁹, Asuteka Nagao¹, Mikako Shirouzu⁶, Akimitsu Okamoto¹, Matthew K Waldor^{10

11

12}, Tsutomu Suzuki¹³

Affiliations

¹ Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
² Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Microbiology, Harvard Medical School, Boston, MA, USA.
⁴ Howard Hughes Medical Institute, Boston, MA, USA.
⁵ Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
⁶ Laboratory for Protein Functional and Structural Biology, RIKEN Center for Biosystems Dynamics Research, Yokohama, Japan.
⁷ Department of Biochemistry, Chulalongkorn University, Bangkok, Thailand.
⁸ Department of Biomolecular Engineering, Nagoya University, Nagoya, Japan.
⁹ Graduate School of Horticulture, Chiba University, Matsudo, Japan.
¹⁰ Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA. mwaldor@bwh.harvard.edu.
¹¹ Department of Microbiology, Harvard Medical School, Boston, MA, USA. mwaldor@bwh.harvard.edu.
¹² Howard Hughes Medical Institute, Boston, MA, USA. mwaldor@bwh.harvard.edu.
¹³ Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan. ts@chembio.t.u-tokyo.ac.jp.

^# Contributed equally.

PMID: 39300229
DOI: 10.1038/s41589-024-01726-x

Abstract

Modified tRNA anticodons are critical for proper mRNA translation during protein synthesis. It is generally thought that almost all bacterial tRNAs^Ile 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^Ile from plant organelles and a subset of bacteria contain a new cytidine derivative, designated 2-aminovaleramididine (ava²C). Like L34, ava²C34 governs both Ile-charging ability and AUA decoding. Cryo-electron microscopy structural analyses revealed molecular details of codon recognition by ava²C34 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.

Abstract

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