Essentiality of Threonylcarbamoyladenosine (t(6)A), a Universal TRNA Modification, in Bacteria
Overview
Molecular Biology
Authors
Affiliations
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.
Liu Y, Yang X, Zhou J, Yang H, Yang R, Zhu P Nat Commun. 2024; 15(1):10479.
PMID: 39622811 PMC: 11612026. DOI: 10.1038/s41467-024-54905-8.
Bollati M, Fasola E, Pieraccini S, Freddi F, Cocomazzi P, Oliva F J Pept Sci. 2024; 31(2):e3658.
PMID: 39434676 PMC: 11669939. DOI: 10.1002/psc.3658.
A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis.
Miyauchi K, Kimura S, Akiyama N, Inoue K, Ishiguro K, Vu T Nat Chem Biol. 2024; .
PMID: 39300229 DOI: 10.1038/s41589-024-01726-x.
Delgado S, Armijo A, Bravo V, Orellana O, Salazar J, Katz A Front Microbiol. 2024; 15:1412318.
PMID: 39161601 PMC: 11332805. DOI: 10.3389/fmicb.2024.1412318.
tRNA Modifications and Dysregulation: Implications for Brain Diseases.
Lv X, Zhang R, Li S, Jin X Brain Sci. 2024; 14(7).
PMID: 39061374 PMC: 11274612. DOI: 10.3390/brainsci14070633.