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Essentiality of Threonylcarbamoyladenosine (t(6)A), a Universal TRNA Modification, in Bacteria

Abstract

Threonylcarbamoyladenosine (t(6)A) is a modified nucleoside universally conserved in tRNAs in all three kingdoms of life. The recently discovered genes for t(6)A 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 t(6)A 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 tRNA(Ile)-lysidine synthetase. We confirm that t(6)A is essential in Escherichia coli and a survey of genome-wide essentiality studies shows that genes for t(6)A synthesis are essential in most prokaryotes. This essentiality phenotype is not universal in Bacteria as t(6)A is dispensable in Deinococcus radiodurans, Thermus thermophilus, Synechocystis PCC6803 and Streptococcus mutans. Proteomic analysis of t(6)A(-) D. radiodurans strains revealed an induction of the proteotoxic stress response and identified genes whose translation is most affected by the absence of t(6)A in tRNAs. Thus, although t(6)A is universally conserved in tRNAs, its role in translation might vary greatly between organisms.

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References
1.
Chaudhuri R, Allen A, Owen P, Shalom G, Stone K, Harrison M . Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH). BMC Genomics. 2009; 10:291. PMC: 2721850. DOI: 10.1186/1471-2164-10-291. View

2.
Nureki O, Niimi T, Muramatsu T, Kanno H, Kohno T, Florentz C . Molecular recognition of the identity-determinant set of isoleucine transfer RNA from Escherichia coli. J Mol Biol. 1994; 236(3):710-24. DOI: 10.1006/jmbi.1994.1184. View

3.
Ibba M, Curnow A, Bono J, Rosa P, Woese C, Soll D . Archaeal aminoacyl-tRNA synthesis: unique determinants of a universal genetic code?. Biol Bull. 1999; 196(3):335-6; discussion 336-7. DOI: 10.2307/1542964. View

4.
Gu C, Begley T, Dedon P . tRNA modifications regulate translation during cellular stress. FEBS Lett. 2014; 588(23):4287-96. PMC: 4403629. DOI: 10.1016/j.febslet.2014.09.038. View

5.
Pomerantz S, McCloskey J . Analysis of RNA hydrolyzates by liquid chromatography-mass spectrometry. Methods Enzymol. 1990; 193:796-824. DOI: 10.1016/0076-6879(90)93452-q. View