ArticlemBio2014
Relaxed substrate specificity leads to extensive tRNA mischarging by Streptococcus pneumoniae class I and class II aminoacyl-tRNA synthetases.
Article in mBio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Nanopore sequencing of intact aminoacylated tRNAs.Nature communications · 2025Article
- In vivo proteomics identifies the competence regulon and AliB oligopeptide transporter as pathogenic factors in pneumococcal meningitis.PLoS pathogens · 2019Article
- A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia.Nature communications · 2018Article
- Quality Control by Isoleucyl-tRNA Synthetase of Bacillus subtilis Is Required for Efficient Sporulation.Scientific reports · 2017Article
- Coding of Class I and II Aminoacyl-tRNA Synthetases.Advances in experimental medicine and biology · 2017Review
- Translation quality control is critical for bacterial responses to amino acid stress.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Essentiality of threonylcarbamoyladenosine (t(6)A), a universal tRNA modification, in bacteria.Molecular microbiology · 2015Article
- Bacterial transfer RNAs.FEMS microbiology reviews · 2015Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledAminoacyl-tRNA synthetases provide the first step in protein synthesis quality control by discriminating cognate from noncognate amino acid and tRNA substrates. While substrate specificity is enhanced in many instances by cis- and trans-editing pathways, it has been revealed that in organisms such as Streptococcus pneumoniae some aminoacyl-tRNA synthetases display significant tRNA mischarging activity. To investigate the extent of tRNA mischarging in this pathogen, the aminoacylation profiles of class I isoleucyl-tRNA synthetase (IleRS) and class II lysyl-tRNA synthetase (LysRS) were determined. Pneumococcal IleRS mischarged tRNA(Ile) with both Val, as demonstrated in other bacteria, and Leu in a tRNA sequence-dependent manner. IleRS substrate specificity was achieved in an editing-independent manner, indicating that tRNA mischarging would only be significant under growth conditions where Ile is depleted. Pneumococcal LysRS was found to misaminoacylate tRNA(Lys) with Ala and to a lesser extent Thr and Ser, with mischarging efficiency modulated by the presence of an unusual U4:G69 wobble pair in the acceptor stems of both pneumococcal tRNA(Lys) isoacceptors. Addition of the trans-editing factor MurM, which also functions in peptidoglycan synthesis, reduced Ala-tRNA(Lys) production by LysRS, providing evidence for cross talk between the protein synthesis and cell wall biogenesis pathways. Mischarging of tRNA(Lys) by AlaRS was also observed, and this would provide additional potential MurM substrates. More broadly, the extensive mischarging activities now described for a number of Streptococcus pneumoniae aminoacyl-tRNA synthetases suggest that adaptive misaminoacylation may contribute significantly to the viability of this pathogen during amino acid starvation. IMPORTANCE: Streptococcus pneumoniae is a common causative agent of several debilitating and potentially life-threatening infections, such as pneumonia, meningitis, and infectious endocarditis. Such infections are increasingly difficult to treat due to widespread development of penicillin resistance. High-level penicillin resistance is known to depend in part upon MurM, a protein involved in both aminoacyl-tRNA-dependent synthesis of indirect amino acid cross-linkages within cell wall peptidoglycan and in translation quality control. The involvement of MurM in both protein synthesis and antibiotic resistance identify it as a potential target for the development of new and potent antibiotics for pneumococcal infections. The goals of this work were to identify and characterize S. pneumoniae pathways that can synthesize mischarged tRNAs and to relate these activities to expected changes in protein and peptidoglycan biosynthesis during antibiotic and nutritional stress.
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