VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
复制标题
结核分枝杆菌的 VapC20 裂解 23S rRNA 的 Sarcin-Ricin 环
DOI：
10.1038/ncomms3796
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发表时间：
2013
影响因子：
16.6
通讯作者：
K. Gerdes
中科院分区：
文献类型：
--
作者：
K. Winther;D. Brodersen;Alistair K. Brown;K. Gerdes
高度持久和经常致命的人类病原体结核分枝杆菌含有至少88个毒素-抗毒素基因。其中一半以上编码VapC PIN结构域核糖核酸内切酶，以未知的机制抑制细胞生长。本研究表明，结核分枝杆菌的VapC20通过切割Sarcin - ricin环（SRL） 23S核糖体RNA来抑制翻译，其位置与Sarcin和其他真核核素毒素切割的位置相同。受毒素抑制的细胞可以通过抗毒素的表达而获救，从而提高了vapC20参与结核分枝杆菌表现出的极端持久性的可能性。vpc20的切割被SRL的突变所抑制，这些突变位于切割位点的侧面，而不是环中其他地方的变化。SRL茎的断裂消除了卵裂；然而，恢复SRL茎结构的进一步突变恢复了切割，揭示了SRL的结构而不是确切的序列对这种活性很重要。毒素-抗毒素系统与结核分枝杆菌的致病性有关。在这里，作者研究了结核分枝杆菌毒素VapC20的功能，并表明它可以通过切割23S rRNA的Sarcin-Ricin环来破坏蛋白质翻译并抑制细菌生长
The highly persistent and often lethal human pathogen, Mycobacterium tuberculosis contains at least 88 toxin–antitoxin genes. More than half of these encode VapC PIN domain endoribonucleases that inhibit cell growth by unknown mechanisms. Here we show that VapC20 of M. tuberculosis inhibits translation by cleavage of the Sarcin–Ricin loop (SRL) of 23S ribosomal RNA at the same position where Sarcin and other eukaryotic ribotoxins cleave. Toxin-inhibited cells can be rescued by the expression of the antitoxin, thereby raising the possibility that vapC20 contributes to the extreme persistence exhibited by M. tuberculosis. VapC20 cleavage is inhibited by mutations in the SRL that flank the cleavage site but not by changes elsewhere in the loop. Disruption of the SRL stem abolishes cleavage; however, further mutations that restore the SRL stem structure restore cleavage, revealing that the structure rather than the exact sequence of the SRL is important for this activity. Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
影响因子：
16
作者：
Sberro, Hila;Leavitt, Azita;Kiro, Ruth;Koh, Eugene;Peleg, Yoav;Qimron, Udi;Sorek, Rotem
通讯作者：
Sorek, Rotem
影响因子：
5.6
作者：
Shi, Xinying;Khade, Prashant K.;Sanbonmatsu, Karissa Y.;Joseph, Simpson
通讯作者：
Joseph, Simpson