Transcriptional Frameshifting Rescues Citrobacter rodentium Type VI Secretion by the Production of Two Length Variants from the Prematurely Interrupted tssM Gene

The Type VI secretion system (T6SS) mediates toxin delivery into both eukaryotic and prokaryotic cells. It is composed of a cytoplasmic structure resembling the tail of contractile bacteriophages anchored to the cell envelope through a membrane complex composed of the TssL and TssM inner membrane proteins and of the TssJ outer membrane lipoprotein. The C-terminal domain of TssM is required for its interaction with TssJ, and for the function of the T6SS. In Citrobacter rodentium, the tssM1 gene does not encode the C-terminal domain. However, the stop codon is preceded by a run of 11 consecutive adenosines. In this study, we demonstrate that this poly-A tract is a transcriptional slippery site that induces the incorporation of additional adenosines, leading to frameshifting, and hence the production of two TssM1 variants, including a full-length canonical protein. We show that both forms of TssM1, and the ratio between these two forms, are required for the function of the T6SS in C. rodentium. Finally, we demonstrate that the tssM gene associated with the Yersinia pseudotuberculosis T6SS-3 gene cluster is also subjected to transcriptional frameshifting.

六型分泌系统（Type VI secretion system, T6SS）可介导毒素递送至真核与原核细胞内。该系统由一类类似收缩性噬菌体尾部的胞质结构组成，该结构通过由TssL、TssM内膜蛋白与TssJ外膜脂蛋白构成的膜复合物锚定在细胞被膜上。TssM的C端结构域是其与TssJ相互作用以及六型分泌系统发挥功能所必需的。在鼠柠檬酸杆菌（Citrobacter rodentium）中，tssM1基因并不编码C端结构域，但其终止密码子上游存在一段由11个连续腺苷串联而成的序列。本研究证实，该多腺苷酸序列属于转录滑动位点，可诱导额外腺苷的掺入，进而引发移码突变，最终产生两种TssM1变体，其中包含全长的经典蛋白。研究表明，两种形式的TssM1及其表达比例，对于鼠柠檬酸杆菌中六型分泌系统的功能均不可或缺。最后，本研究证实，与假结核耶尔森菌（Yersinia pseudotuberculosis）T6SS-3基因簇相关的tssM基因同样存在转录移码现象。