TY - JOUR
T1 - GNAT toxins evolve toward narrow tRNA target specificities
AU - Bikmetov, Dmitry
AU - Hall, Alexander M.J.
AU - Livenskyi, Alexei
AU - Gollan, Bridget
AU - Ovchinnikov, Stepan
AU - Gilep, Konstantin
AU - Kim, Jenny Y.
AU - Larrouy-Maumus, Gerald
AU - Zgoda, Viktor
AU - Borukhov, Sergei
AU - Severinov, Konstantin
AU - Helaine, Sophie
AU - Dubiley, Svetlana
N1 - Publisher Copyright:
© 2022 The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2022/6/10
Y1 - 2022/6/10
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkac356
DO - 10.1093/nar/gkac356
M3 - Article
C2 - 35609997
AN - SCOPUS:85131771917
SN - 0305-1048
VL - 50
SP - 5807
EP - 5817
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 10
ER -