HicA of Escherichia coli Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea
HicA of Escherichia coli Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea
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DOI：
10.1128/jb.01013-08
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发表时间：
2009-02-15
影响因子：
3.2
通讯作者：
Gerdes, Kenn
中科院分区：
文献类型：
--
作者：
Jorgensen, Mikkel G.;Pandey, Deo P.;Gerdes, Kenn
毒素-抗毒素（TA）基因座在自由生活的细菌和古细菌中很常见。TA基因座编码稳定的毒素，其被代谢不稳定的抗毒素中和。抗毒素可以是蛋白质或反义RNA。到目前为止，已经鉴定出六个不同的TA基因家族，其中抗毒素是蛋白质。最近，Makarova等人（K. S. Makarova，N. V. Grishin和E. Koonin，Bioinformatics 22：2581-2584，2006）提出hicAB基因座构成新的TA基因家族。使用大肠杆菌K-12的hicAB位点作为模型系统，我们提出了支持这一推论的证据：小HicA蛋白（58个氨基酸[aa]）的表达诱导三种模型mRNA和tmRNA的切割。与此同时，全球翻译率大幅下降。使用tmRNA作为底物，我们表明，HicA诱导的切割不需要靶RNA被翻译。HicB（145 aa）的表达阻止了HicA介导的细胞生长抑制。这些结果表明HicB中和HicA，因此起抗毒素的作用。与其他抗毒素（RelB和MazF）一样，HicB可以使HicA抑制的细胞复苏，表明HicA的异位产生诱导抑菌而非杀菌条件。营养饥饿诱导强烈的hicAB转录依赖于Lon蛋白酶。对218个原核生物基因组的挖掘表明，hicAB位点在细菌和古细菌中非常丰富。
Toxin-antitoxin (TA) loci are common in free-living bacteria and archaea. TA loci encode a stable toxin that is neutralized by a metabolically unstable antitoxin. The antitoxin can be either a protein or an antisense RNA. So far, six different TA gene families, in which the antitoxins are proteins, have been identified. Recently, Makarova et al. (K. S. Makarova, N. V. Grishin, and E. V. Koonin, Bioinformatics 22:2581-2584, 2006) suggested that the hicAB loci constitute a novel TA gene family. Using the hicAB locus of Escherichia coli K-12 as a model system, we present evidence that supports this inference: expression of the small HicA protein (58 amino acids [aa]) induced cleavage in three model mRNAs and tmRNA. Concomitantly, the global rate of translation was severely reduced. Using tmRNA as a substrate, we show that HicA-induced cleavage does not require the target RNA to be translated. Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an antitoxin. As with other antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces a bacteriostatic rather than a bactericidal condition. Nutrient starvation induced strong hicAB transcription that depended on Lon protease. Mining of 218 prokaryotic genomes revealed that hicAB loci are abundant in bacteria and archaea.