Translation-targeting toxic small alarmone synthetases (toxSAS) are effectors of bacterial toxin-antitoxin systems that pyrophosphorylate the 3′-CCA end of transfer RNA (tRNA) to prevent aminoacylation. toxSAS are implicated in antiphage immunity: Phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNA Gly and tRNA Thr . The first, second, fourth, and fifth base pairs of the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRel SJ46 differ in tRNA specificity from FaRel2 and rationalize this through structural modeling: While the universal 3′-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defenses, we hypothesize that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.

中文翻译：

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毒性小警报酮合成酶 FaRel2 通过热磷酸化 tRNA Gly 和 tRNA Thr 抑制翻译


翻译靶向毒性小警报酮合成酶 （toxSAS） 是细菌毒素-抗毒素系统的效应子，可焦磷酸化转移 RNA （tRNA） 的 3′-CCA 末端以防止氨酰化。toxSAS 与抗噬菌体免疫有关：噬菌体检测触发 toxSAS 活性以关闭病毒生产。我们表明 toxSAS FaRel2 检查 tRNA 受体茎以特异性选择 tRNA Gly 和 tRNA Thr。茎的第一、第二、第四和第五碱基对充当特异性决定因素。我们表明 toxSASs PhRel2 和 CapRel SJ46 在 tRNA 特异性上与 FaRel2 不同，并通过结构建模将其合理化：虽然通用的 3'-CCA 末端插入高度保守的 CCA 识别槽，但受体茎识别区域在 toxSAS 多样性中是可变的。由于噬菌体使用 tRNA 同工受体来克服 tRNA 靶向防御，我们假设高度可进化的模块化 tRNA 识别允许通过 tRNA 底物特异性切换逃避病毒对策。