Toxins targeting transfer RNAs: Translation inhibition by bacterial toxin-antitoxin systems.

Toxins targeting transfer RNAs: Translation inhibition by bacterial toxin-antitoxin systems.
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DOI:
10.1002/wrna.1506
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发表时间:
2019-01
期刊:
Wiley interdisciplinary reviews. RNA
影响因子:
--
通讯作者:
Butler JS
Butler JS
中科院分区:
其他
文献类型:
--
作者:
Walling LR;Butler JS

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前毒素-抗毒素系统由蛋白质毒素及其同源抗毒素组成。这些系统在细菌和古生菌中大量存在,并在生长调节中发挥重要作用。在有利的生长条件下,抗毒素中和毒素的活性。然而,在胁迫或饥饿条件下,抗毒素失活,释放毒素以抑制生长并导致休眠。几种毒素-抗毒素系统使用的生长抑制机制之一是通过阻止氨酰化、乙酰化伯氨基或内切核酸裂解靶向tRNA。所有这些机制都抑制翻译并导致生长停滞。这些毒素中的许多毒素仅作用于特定的tRNA或特定的tRNA子集,但是需要更多的工作来了解这些毒素的特异性决定因素。对于其特异性已被表征的毒素,tRNA的序列和结构组分对于毒素的识别都很重要。关于休眠细菌在毒素诱导后恢复生长的机制也存在问题。tmRNAs拯救停滞的核糖体,从tRNAs中去除乙酰化的氨基,或连接切割的RNA片段都被认为是逆转毒素诱导的休眠的机制。然而,大多数tRNA靶向毒素诱导后恢复生长的机制尚不清楚。细菌毒素-抗毒素系统使用各种机制通过靶向tRNA来抑制翻译和阻止生长。
Prokaryotic toxin-antitoxin systems are composed of a protein toxin and its cognate antitoxin. These systems are abundant in bacteria and archaea and play an important role in growth regulation. During favourable growth conditions, the antitoxin neutralizes the toxin’s activity. However, during conditions of stress or starvation, the antitoxin is inactivated, freeing the toxin to inhibit growth and resulting in dormancy. One mechanism of growth inhibition used by several toxin-antitoxin systems results from targeting tRNAs, either through preventing aminoacylation, acetylating the primary amino group, or endonucleolytic cleavage. All of these mechanisms inhibit translation and result in growth arrest. Many of these toxins only act on a specific tRNA or a specific subset of tRNAs, however more work is necessary to understand the specificity determinants of these toxins. For the toxins whose specificity has been characterized, both sequence and structural components of the tRNA appear important for recognition by the toxin. Questions also remain regarding the mechanisms used by dormant bacteria to resume growth after toxin induction. Rescue of stalled ribosomes by tmRNAs, removal of acetylated amino groups from tRNAs, or ligation of cleaved RNA fragments have all been implicated as mechanisms for reversing toxin-induced dormancy. However, the mechanisms of resuming growth after induction of the majority of tRNA targeting toxins are not yet understood. Bacterial toxin-antitoxin systems use various mechanisms to inhibit translation and arrest growth by targeting tRNAs.
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