Essentiality of threonylcarbamoyladenosine (t6A), a universal tRNA modification,in bacteria |
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| Authors: | Caroline Köhrer Jennifer J Thiaville Chris Deutsch Dirk Iwata‐Reuyl Jo Marie Bacusmo Jean Armengaud Yoshitaka Bessho Collin Wetzel Xiaoyu Cao Patrick A Limbach Uttam L RajBhandary Valérie de Crécy‐Lagard |
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| Institution: | 1. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA;2. Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA;3. Department of Chemistry, Portland State University, Portland, OR, USA;4. CEA, DSV, IBiTec‐S, SPI, Li2D, Laboratory ‘Innovative technologies for Detection and Diagnostics’, Bagnols‐sur‐Cèze, France;5. RIKEN SPring‐8 Center, Sayo, Hyogo, Japan;6. Institute of Physics, Academia Sinica, Taipei, Taiwan;7. Rieveschl Laboratories for Mass Spectrometry, Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA;8. University of Florida Genetics Institute, University of Florida, Gainesville, FL, USA |
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| Abstract: | Threonylcarbamoyladenosine (t6A) is a modified nucleoside universally conserved in tRNAs in all three kingdoms of life. The recently discovered genes for t6A synthesis, including tsaC and tsaD, are essential in model prokaryotes but not essential in yeast. These genes had been identified as antibacterial targets even before their functions were known. However, the molecular basis for this prokaryotic‐specific essentiality has remained a mystery. Here, we show that t6A is a strong positive determinant for aminoacylation of tRNA by bacterial‐type but not by eukaryotic‐type isoleucyl‐tRNA synthetases and might also be a determinant for the essential enzyme tRNAIle‐lysidine synthetase. We confirm that t6A is essential in Escherichia coli and a survey of genome‐wide essentiality studies shows that genes for t6A synthesis are essential in most prokaryotes. This essentiality phenotype is not universal in Bacteria as t6A is dispensable in Deinococcus radiodurans, Thermus thermophilus, Synechocystis PCC6803 and Streptococcus mutans. Proteomic analysis of t6A? D. radiodurans strains revealed an induction of the proteotoxic stress response and identified genes whose translation is most affected by the absence of t6A in tRNAs. Thus, although t6A is universally conserved in tRNAs, its role in translation might vary greatly between organisms. |
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