文章基本信息

标题：Mg2+ regulates transcription of mgtA in Salmonella Typhimurium via translation of proline codons during synthesis of the MgtL peptide
本地全文：下载
作者：Aaron R. Gall ; Kirill A. Datsenko ; Nara Figueroa-Bossi 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：52
页码：15096-15101
DOI：10.1073/pnas.1612268113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMg2+ is an important signal for the regulation of virulence and thermotolerance in Salmonella enterica. Transcription of the mgtA gene, which encodes a transporter for Mg2+, is highly induced by Mg2+ limitation. The 5' leader of the mgtA mRNA encodes mgtL, a 17-codon, proline-rich open reading frame, whose translation controls the transcription of mgtA: efficient translation of mgtL results in termination of transcription upstream of the mgtA protein-coding region, whereas slow or incomplete translation of mgtL antagonizes this termination. We show that the proline codons in mgtL present an impediment to translation at low but not high Mg2+ concentrations, and thereby, we provide a model for how Mg2+ is coupled to the regulation of mgtA transcription. In Salmonella enterica serovar Typhimurium, Mg2+ limitation induces transcription of the mgtA Mg2+ transport gene, but the mechanism involved is unclear. The 5' leader of the mgtA mRNA contains a 17-codon, proline-rich ORF, mgtL, whose translation regulates the transcription of mgtA [Park S-Y et al. (2010) Cell 142:737-748]. Rapid translation of mgtL promotes formation of a secondary structure in the mgtA mRNA that permits termination of transcription by the Rho protein upstream of mgtA, whereas slow or incomplete translation of mgtL generates a different structure that blocks termination. We identified the following mutations that conferred high-level transcription of mgtA at high [Mg2+]: (i) a base-pair change that introduced an additional proline codon into mgtL, generating three consecutive proline codons; (ii) lesions in rpmA and rpmE, which encode ribosomal proteins L27 and L31, respectively; (iii) deletion of efp, which encodes elongation factor EF-P that assists the translation of proline codons; and (iv) a heat-sensitive mutation in trmD, whose product catalyzes the m1G37 methylation of tRNAPro. Furthermore, substitution of three of the four proline codons in mgtL rendered mgtA uninducible. We hypothesize that the proline codons present an impediment to the translation of mgtL, which can be alleviated by high [Mg2+] exerted on component(s) of the translation machinery, such as EF-P, TrmD, or a ribosomal factor. Inadequate [Mg2+] precludes this alleviation, making mgtL translation inefficient and thereby permitting mgtA transcription. These findings are a significant step toward defining the target of Mg2+ in the regulation of mgtA transcription.
关键词：MgtA Mg²⁺ transporter ; MgtL leader peptide ; 50S ribosomal proteins ; EF-P translation factor ; TrmD methyltransferase