A transfer RNA inosine modification drives genome-wide synonymous recoding across human commensal bacterial families
Abstract Inosine modification on tRNA anticodon (I34) is universally conserved in three kingdoms of life and critical to tRNA decoding capabilities. We found that tRNALeu(IAG) in commensal human bacterial families in Lactobaccilalles is concurrent with genome-wide synonymous leucine codon reprogramming. Pathway analysis reveals significant synonymous Leu codon changes in proteins in multiple KEGG pathways on cellular metabolism, where many genome-wide dominant UUA in families without tRNALeu(IAG) is reprogrammed to CUU, CUC and UUG in families with tRNALeu(IAG). We provide biochemical and phenotypic results to support mechanisms that enable synonymous Leu codon substitutions to confer greater translation equivalency and growth fitness, indicating that a tRNA inosine modification can propel the genome-wide evolution of synonymous leucine codons.
Authors
- Amy D. Willis (ORCID: https://orcid.org/0000-0002-2802-4317)
- Kristin S. Koutmou (ORCID: https://orcid.org/0000-0002-7763-9262)
- T.J. Smith (ORCID: https://orcid.org/0000-0001-8444-6808)
- Mohammad Amin Bayat Tork (ORCID: https://orcid.org/0000-0002-2944-046X)
- Yichen Hou (ORCID: https://orcid.org/0000-0002-6347-3636)
- Karen Lolans (ORCID: https://orcid.org/0000-0003-1903-756X)
- Chathuri Pathirage (ORCID: https://orcid.org/0000-0003-1527-0882)
- Weixin Tang (ORCID: https://orcid.org/0000-0002-5739-5416)
- Christopher D. Katanski (ORCID: https://orcid.org/0000-0002-1707-081X)
- Yuan Wu (ORCID: https://orcid.org/0000-0003-2262-9494)
- Marcus Foo
- Hoang Anh V Tran (ORCID: https://orcid.org/0009-0000-6373-3859)
- A Murat Eren (ORCID: https://orcid.org/0000-0001-9013-4827)
- Iva Veseli (ORCID: https://orcid.org/0000-0003-2390-5286)
- Dominika Rudzka
- Wen Zhang (ORCID: https://orcid.org/0000-0001-8577-2613)
- Michael Federle (ORCID: https://orcid.org/0000-0002-4554-543X)
- Tao Pan (ORCID: https://orcid.org/0000-0003-1096-8405)
- Jennifer C Chang (ORCID: https://orcid.org/0000-0002-6175-1284)
Institutions
- Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung (DE)
- Carl von Ossietzky Universität Oldenburg (DE)
- University of Washington (US)
- University of Michigan (US)
- University of Illinois Chicago (US)
- University of Chicago (US)
- Helmholtz Institute for Functional Marine Biodiversity (DE)
- Max Planck Institute for Marine Microbiology (DE)
- Meso (United States) (US)
Publication Details
- Journal
- PNAS Nexus
- Published
- 2026-05-30
- DOI
- https://doi.org/10.1093/pnasnexus/pgag187
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00