tRNA methylation resolves codon usage bias at the limit of cell viability

Isao Masuda, Yuka Yamaki, Rajesh Detroja, Somnath Tagore, Henry Moore, Sunita Maharjan, Yuko Nakano, Thomas Christian, Ryuma Matsubara, Todd M. Lowe, Milana Frenkel-Morgenstern, Ya Ming Hou

Research output: Contribution to journalArticlepeer-review


Codon usage of each genome is closely correlated with the abundance of tRNA isoacceptors. How codon usage bias is resolved by tRNA post-transcriptional modifications is largely unknown. Here we demonstrate that the N1-methylation of guanosine at position 37 (m1G37) on the 3′-side of the anticodon, while not directly responsible for reading of codons, is a neutralizer that resolves differential decoding of proline codons. A genome-wide suppressor screen of a non-viable Escherichia coli strain, lacking m1G37, identifies proS suppressor mutations, indicating a coupling of methylation with tRNA prolyl-aminoacylation that sets the limit of cell viability. Using these suppressors, where prolyl-aminoacylation is decoupled from tRNA methylation, we show that m1G37 neutralizes differential translation of proline codons by the major isoacceptor. Lack of m1G37 inactivates this neutralization and exposes the need for a minor isoacceptor for cell viability. This work has medical implications for bacterial species that exclusively use the major isoacceptor for survival.

Original languageEnglish
Article number111539
JournalCell Reports
Issue number4
StatePublished - 25 Oct 2022


  • CP: Microbiology
  • CP: Molecular biology
  • Pro codons CC[C/U]
  • Pro(GGG)
  • Pro(UGG)
  • TrmD
  • aminoacylation with proline
  • cmoU34
  • mG37-tRNA
  • proS
  • suppressor screens

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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