A transfer RNA inosine modification drives genome-wide synonymous recoding across human commensal bacterial families

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ID: 315206
2026
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Abstract
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.
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openalex_W7162793954 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Christopher D. Katanski, Chathuri Pathirage, Jennifer C Chang, Iva Veseli, T.J. Smith, Marcus Foo, Yuan Wu, Yichen Hou, Hoang Anh V Tran, Dominika Rudzka, Wen Zhang, Mohammad Amin Bayat Tork, Karen Lolans, Amy D. Willis, Weixin Tang, A Murat Eren, Michael Federle, Kristin S. Koutmou, Tao Pan
Journal PNAS nexus
Year 2026
DOI
10.1093/pnasnexus/pgag187
URL
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