Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor-specific tRNase.
Growth-regulating Mycobacterium tuberculosis VapC-mt4 toxin is an isoacceptor-specific tRNase.
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DOI：
10.1038/ncomms8480
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发表时间：
2015-07-09
影响因子：
16.6
通讯作者：
Woychik NA
中科院分区：
文献类型：
--
作者：
Cruz JW;Sharp JD;Hoffer ED;Maehigashi T;Vvedenskaya IO;Konkimalla A;Husson RN;Nickels BE;Dunham CM;Woychik NA
毒素-抗毒素(TA)系统与细菌细胞生长下调有关，与应激生存和潜伏的结核病感染有关，但这些TA毒素的活性和细胞内靶点很大程度上尚不清楚。在这里，我们使用一种专门的RNA-seq方法来识别结核分枝杆菌VapC TA毒素VapC-MT4(也称为VapC4)的靶标，这些靶标用传统方法无法检测到。与结核分枝杆菌的另一种特有的VapC毒素不同，VapC-MT4在sarcin-ricin环处切割23S rRNA，VapC-MT4选择性地靶向45个结核分枝杆菌tRNAs中的三个(tRNAAla2、tRNASer26和tRNASer24)，在其反密码子或其附近切割，导致tRNA一半的产生。虽然tRNA切割有时被列为细菌的宿主防御机制，但VapC-MT4相反地改变特定的tRNA来抑制翻译和调节生长。VapC-MT4的这种与压力相关的活性反映了真核细胞tRNase的基本特征，这些tRNase也产生tRNA的一半并抑制翻译以响应压力。
Toxin–antitoxin (TA) systems are implicated in the downregulation of bacterial cell growth associated with stress survival and latent tuberculosis infection, yet the activities and intracellular targets of these TA toxins are largely uncharacterized. Here, we use a specialized RNA-seq approach to identify targets of a Mycobacterium tuberculosis VapC TA toxin, VapC-mt4 (also known as VapC4), which have eluded detection using conventional approaches. Distinct from the one other characterized VapC toxin in M. tuberculosis that cuts 23S rRNA at the sarcin–ricin loop, VapC-mt4 selectively targets three of the 45 M. tuberculosis tRNAs (tRNAAla2, tRNASer26 and tRNASer24) for cleavage at, or adjacent to, their anticodons, resulting in the generation of tRNA halves. While tRNA cleavage is sometimes enlisted as a bacterial host defense mechanism, VapC-mt4 instead alters specific tRNAs to inhibit translation and modulate growth. This stress-linked activity of VapC-mt4 mirrors basic features of eukaryotic tRNases that also generate tRNA halves and inhibit translation in response to stress.