GNAT toxins evolve toward narrow tRNA target specificities

Dmitry Bikmetov, Alexander M.J. Hall, Alexei Livenskyi, Bridget Gollan, Stepan Ovchinnikov, Konstantin Gilep, Jenny Y. Kim, Gerald Larrouy-Maumus, Viktor Zgoda, Sergei Borukhov, Konstantin Severinov, Sophie Helaine, Svetlana Dubiley

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Type II toxin-antitoxin (TA) systems are two-gene modules widely distributed among prokaryotes. GNAT toxins associated with the DUF1778 antitoxins represent a large family of type II TAs. GNAT toxins inhibit cell growth by disrupting translation via acetylation of aminoacyl-tRNAs. In this work, we explored the evolutionary trajectory of GNAT toxins. Using LC/MS detection of acetylated aminoacyl-tRNAs combined with ribosome profiling, we systematically investigated the in vivo substrate specificity of an array of diverse GNAT toxins. Our functional data show that the majority of GNAT toxins are specific to Gly-tRNA isoacceptors. However, the phylogenetic analysis shows that the ancestor of GNAT toxins was likely a relaxed specificity enzyme capable of acetylating multiple elongator tRNAs. Together, our data provide a remarkable snapshot of the evolution of substrate specificity.

Original languageEnglish (US)
Pages (from-to)5807-5817
Number of pages11
JournalNucleic acids research
Issue number10
StatePublished - Jun 10 2022

All Science Journal Classification (ASJC) codes

  • Genetics


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