{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:35:12Z","timestamp":1772768112956,"version":"3.50.1"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,9,9]],"date-time":"2014-09-09T00:00:00Z","timestamp":1410220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,10,31]],"date-time":"2014-10-31T00:00:00Z","timestamp":1414713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Aminoacyl-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\n            <jats:italic>cis-<\/jats:italic>\n            and\n            <jats:italic>trans<\/jats:italic>\n            -editing pathways, it has been revealed that in organisms such as\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            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\n            <jats:sup>Ile<\/jats:sup>\n            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\n            <jats:sup>Lys<\/jats:sup>\n            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\n            <jats:sup>Lys<\/jats:sup>\n            isoacceptors. Addition of the\n            <jats:italic>trans-<\/jats:italic>\n            editing factor MurM, which also functions in peptidoglycan synthesis, reduced Ala-tRNA\n            <jats:sup>Lys<\/jats:sup>\n            production by LysRS, providing evidence for cross talk between the protein synthesis and cell wall biogenesis pathways. Mischarging of tRNA\n            <jats:sup>Lys<\/jats:sup>\n            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\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            aminoacyl-tRNA synthetases suggest that adaptive misaminoacylation may contribute significantly to the viability of this pathogen during amino acid starvation.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:named-content content-type=\"genus-species\">Streptococcus pneumoniae<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">S. pneumoniae<\/jats:named-content>\n            pathways that can synthesize mischarged tRNAs and to relate these activities to expected changes in protein and peptidoglycan biosynthesis during antibiotic and nutritional stress.\n          <\/jats:p>","DOI":"10.1128\/mbio.01656-14","type":"journal-article","created":{"date-parts":[[2014,9,10]],"date-time":"2014-09-10T00:27:13Z","timestamp":1410308833000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Relaxed Substrate Specificity Leads to Extensive tRNA Mischarging by Streptococcus pneumoniae Class I and Class II Aminoacyl-tRNA Synthetases"],"prefix":"10.1128","volume":"5","author":[{"given":"Jennifer","family":"Shepherd","sequence":"first","affiliation":[{"name":"Department of Microbiology and Center for RNA Biology, Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Ibba","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Center for RNA Biology, Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2006.12.016"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00813-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.7.3990-3997.2000"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08576"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000315107"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(99)80033-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2013.01.004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.62.070193.003435"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6603(08)60869-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/347249a0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9084(93)90006-E"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/347203a0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47323-7"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5340.1119"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.617"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.5.1189"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdf373"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1582"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.015"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073210"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00624a034"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5430.1074"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)45304-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5316.1250"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990629i"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.07.036"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.479824"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970589n"},{"key":"e_1_3_3_30_2","unstructured":"ShepherdJ\n. 2011. 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