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Bacterial translation machinery for deliberate mistranslation of the genetic code

Oscar Vargas-Rodriguez1, Ahmed H Badran2, Kyle S Hoffman3

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511; oscar.vargas@yale.edu dieter.soll@yale.edu.

Proceedings of the National Academy of Sciences of the United States of America
|August 20, 2021
PubMed

Insights

Microbial pathogens deliberately mistranslate their genetic code. Researchers discovered a novel mechanism in plant pathogens where a specific transfer RNA (tRNA) mistranslates alanine codons as proline, creating proteome diversity.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Mistranslation, or inaccurate genetic code expression, is an emerging area in microbial research.
  • Pathogenic microbes may deliberately mistranslate their genetic code to enhance host invasion or immune evasion.
  • Identifying unique mistranslation mechanisms across different pathogen groups presents a significant challenge.

Purpose of the Study:

  • To investigate a novel mistranslation mechanism in microbial pathogens.
  • To characterize the role of duplicated aminoacyl-transfer RNA (tRNA) synthetase genes in mistranslation.
  • To identify and analyze a specific mistranslation system in plant pathogens from the *Streptomyces* genus.

Main Methods:

  • Studied duplicated aminoacyl-transfer RNA (tRNA) synthetase genes, focusing on bacterial prolyl-tRNA synthetase (ProRS).
  • Identified an anomalous ProRS isoform (ProRSx) and a corresponding tRNA (tRNAProA) in *Streptomyces* plant pathogens.
  • Utilized biochemical, genetic, and mass spectrometry techniques to analyze tRNAProA structure and function.

Main Results:

  • Discovered tRNAProA possesses an unusual hybrid structure enabling mistranslation of alanine codons (GCU) into proline.
  • Demonstrated that cells expressing ProRSx and tRNAProA can translate GCU codons as both alanine and proline.
  • Showcased how this dual codon usage generates proteomic diversity through stochastic Ala→Pro mutations.

Conclusions:

  • Identified the first natural tRNA synthetase/tRNA pair dedicated to mistranslating sense codons.
  • Revealed that *Streptomyces* plant pathogens possess a mechanism to alter sense codon identity.
  • Highlighted the potential of mistranslation as a strategy for microbial adaptation and pathogenicity.
Keywords:
Streptomycesaminoacyl-tRNA synthetasegenetic codemistranslationtRNA

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