New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system.
New connections in the prokaryotic toxin-antitoxin network: relationship with the eukaryotic nonsense-mediated RNA decay system.
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DOI：
10.1186/gb-2003-4-12-r81
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发表时间：
2003
期刊：
影响因子：
12.3
通讯作者：
Aravind L
中科院分区：
文献类型：
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作者：
Anantharaman V;Aravind L
对来自不同细菌和古细菌的 RelE 型和 ParE 型分离后细胞杀伤 (PSK) 毒素的序列谱分析将这些蛋白质统一为一个超家族。进一步的比较分析表明，真核无义介导的RNA衰变系统的核心可能是从PSK相关系统进化而来的。一些原核质粒通过不同的分离后细胞杀伤系统在宿主中维持自身。最近的研究结果表明，分离后细胞杀伤系统（例如 RelE 系统）的毒素和抗毒素的染色体编码副本可能在应激条件下发挥调节开关的作用。 RelE 毒素裂解核糖体相关转录物，而另一种分离后细胞杀伤毒素 ParE 则充当旋转酶抑制剂。通过序列分析，我们能够将 RelE 型和 ParE 型毒素与来自不同细菌和古细菌的几个小的、未表征的蛋白质家族统一成一个超家族。基因邻域分析表明，大多数这些蛋白质是由特征邻域中的基因编码的，其中编码毒素的基因总是与编码转录因子（也是抗毒素）的基因同时出现。然而，伴随 RelE/ParE 超家族的转录因子可能属于无关或远亲的超家族。我们使用这种保守的邻域模板来传递搜索基因组并识别新的分离后细胞杀伤相关系统。在几种原核生物中观察到的这些新系统之一含有一种带有 PilT-N 末端 (PIN) 结构域的预测毒素，该毒素也存在于真核无义介导的 RNA 衰变系统的蛋白质中。这些搜索还发现了分离后细胞杀伤系统中的新型转录因子（抗毒素）。此外，毒素文件定义了一个潜在的金属酶超家族，在细菌、古细菌和真核生物中具有新的代表，可能作用于核酸。分离后细胞杀伤相关系统中紧密维持的基因邻域似乎是通过功能等效但进化上不相关的基因原位置换毒素或抗毒素基因而进化的。我们预测，含有 PilT-N 末端结构域毒素和真核无义介导的 RNA 衰变系统的新型分离后细胞杀伤相关系统可能通过共同机制发挥作用，其中 PilT-N 末端结构域裂解核糖体相关转录本。真核生物无义介导的RNA衰变系统的核心可能是从分离后细胞杀伤相关系统进化而来的。
Sequence profile analysis of the RelE- and ParE-type post-segregational cell killing (PSK) toxins from diverse bacteria and archaea has unified these proteins into a single superfamily. Further comparative analysis suggests that the core of the eukaryotic nonsense-mediated RNA decay system has probably evolved from a PSK-related system. Several prokaryotic plasmids maintain themselves in their hosts by means of diverse post-segregational cell killing systems. Recent findings suggest that chromosomally encoded copies of toxins and antitoxins of post-segregational cell killing systems - such as the RelE system - might function as regulatory switches under stress conditions. The RelE toxin cleaves ribosome-associated transcripts, whereas another post-segregational cell killing toxin, ParE, functions as a gyrase inhibitor. Using sequence profile analysis we were able unify the RelE- and ParE-type toxins with several families of small, uncharacterized proteins from diverse bacteria and archaea into a single superfamily. Gene neighborhood analysis showed that the majority of these proteins were encoded by genes in characteristic neighborhoods, in which genes encoding toxins always co-occurred with genes encoding transcription factors that are also antitoxins. The transcription factors accompanying the RelE/ParE superfamily may belong to unrelated or distantly related superfamilies, however. We used this conserved neighborhood template to transitively search genomes and identify novel post-segregational cell killing-related systems. One of these novel systems, observed in several prokaryotes, contained a predicted toxin with a PilT-N terminal (PIN) domain, which is also found in proteins of the eukaryotic nonsense-mediated RNA decay system. These searches also identified novel transcription factors (antitoxins) in post-segregational cell killing systems. Furthermore, the toxin Doc defines a potential metalloenzyme superfamily, with novel representatives in bacteria, archaea and eukaryotes, that probably acts on nucleic acids. The tightly maintained gene neighborhoods of post-segregational cell killing-related systems appear to have evolved by in situ displacement of genes for toxins or antitoxins by functionally equivalent but evolutionarily unrelated genes. We predict that the novel post-segregational cell killing-related systems containing a PilT-N terminal domain toxin and the eukaryotic nonsense-mediated RNA decay system are likely to function via a common mechanism, in which the PilT-N terminal domain cleaves ribosome-associated transcripts. The core of the eukaryotic nonsense-mediated RNA decay system has probably evolved from a post-segregational cell killing-related system.