Mistranslation of the genetic code by a new family of bacterial transfer RNAs.
Mistranslation of the genetic code by a new family of bacterial transfer RNAs.
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DOI：
10.1016/j.jbc.2023.104852
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发表时间：
2023-07
影响因子：
4.8
通讯作者：
Vargas-Rodriguez, Oscar
中科院分区：
文献类型：
--
作者：
Schuntermann, Dominik B.;Fischer, Jonathan T.;Bile, Jonmatthew;Gaier, Sarah A.;Shelley, Brett A.;Awawdeh, Aya;Jahn, Martina;Hoffman, Kyle S.;Westhof, Eric;Soell, Dieter;Clarke, Christopher R.;Vargas-Rodriguez, Oscar
氨基酸与转运rna （trna）的正确偶联对于将遗传信息转化为功能蛋白至关重要。这个过程中的错误导致误译，密码子用错误的氨基酸翻译。虽然不受管制和长期的误译通常是有毒的，但越来越多的证据表明，从细菌到人类的生物体可以诱导并利用误译作为克服不利环境条件的机制。大多数已知的误译病例是由于底物特异性差的翻译因素或底物识别对突变或翻译后修饰等分子变化敏感引起的。在这里，我们报道了两个新的tRNA家族，由链霉菌属和Kitasatospora属的细菌编码，它们通过将反密码子AUU （Asn）或AGU （Thr）整合到一个不同的脯氨酸tRNA结构中而采用双重身份。这些trna通常编码在细菌型脯氨酸- trna合成酶的全长或截断的独特同工异构体旁边。使用两个蛋白质报告器，我们发现这些trna用脯氨酸翻译天冬酰胺和苏氨酸密码子。此外，当在大肠杆菌中表达时，由于全局Asn-to-Pro和Thr-to-Pro突变，trna会导致不同的生长缺陷。然而，tRNA表达诱导的蛋白组内Asn被Pro取代增加了细胞对抗生素carbenicillin的耐受性，这表明Pro错译在某些条件下可能是有益的。总的来说，我们的结果显着扩展了已知具有专用误翻译机制的生物体的目录，并支持误翻译是细胞抵御环境压力的机制的概念。
The correct coupling of amino acids with transfer RNAs (tRNAs) is vital for translating genetic information into functional proteins. Errors during this process lead to mistranslation, where a codon is translated using the wrong amino acid. While unregulated and prolonged mistranslation is often toxic, growing evidence suggests that organisms, from bacteria to humans, can induce and use mistranslation as a mechanism to overcome unfavorable environmental conditions. Most known cases of mistranslation are caused by translation factors with poor substrate specificity or when substrate discrimination is sensitive to molecular changes such as mutations or posttranslational modifications. Here we report two novel families of tRNAs, encoded by bacteria from the Streptomyces and Kitasatospora genera, that adopted dual identities by integrating the anticodons AUU (for Asn) or AGU (for Thr) into the structure of a distinct proline tRNA. These tRNAs are typically encoded next to a full-length or truncated version of a distinct isoform of bacterial-type prolyl-tRNA synthetase. Using two protein reporters, we showed that these tRNAs translate asparagine and threonine codons with proline. Moreover, when expressed in Escherichia coli, the tRNAs cause varying growth defects due to global Asn-to-Pro and Thr-to-Pro mutations. Yet, proteome-wide substitutions of Asn with Pro induced by tRNA expression increased cell tolerance to the antibiotic carbenicillin, indicating that Pro mistranslation can be beneficial under certain conditions. Collectively, our results significantly expand the catalog of organisms known to possess dedicated mistranslation machinery and support the concept that mistranslation is a mechanism for cellular resiliency against environmental stress.
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影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
7.7
作者：
Bullwinkle TJ;Reynolds NM;Raina M;Moghal A;Matsa E;Rajkovic A;Kayadibi H;Fazlollahi F;Ryan C;Howitz N;Faull KF;Lazazzera BA;Ibba M
通讯作者：
Ibba M
影响因子：
14.9
作者：
Lant JT;Kiri R;Duennwald ML;O'Donoghue P
通讯作者：
O'Donoghue P
影响因子：
4.1
作者：
Berg, Matthew D.;Giguere, Daniel J.;Brandl, Christopher J.
通讯作者：
Brandl, Christopher J.
DOI：
10.1073/pnas.1019033108
发表时间：
2011-04-26
影响因子：
11.1
作者：
Jones, Thomas E.;Alexander, Rebecca W.;Pan, Tao
通讯作者：
Pan, Tao