PDF(Pubmed)
Abstract：
Post-transcriptional regulation plays important roles to fine-tune gene expression in bacteria. In particular, regulation of type I toxin-antitoxin (TA) systems is achieved through sophisticated mechanisms involving toxin mRNA folding. Here, we set up a genetic approach to decipher the molecular underpinnings behind the regulation of a type I TA in Helicobacter pylori. We used the lethality induced by chromosomal inactivation of the antitoxin to select mutations that suppress toxicity. We found that single point mutations are sufficient to allow cell survival. Mutations located either in the 5\' untranslated region or within the open reading frame of the toxin hamper its translation by stabilizing stem-loop structures that sequester the Shine-Dalgarno sequence. We propose that these short hairpins correspond to metastable structures that are transiently formed during transcription to avoid premature toxin expression. This work uncovers the co-transcriptional inhibition of translation as an additional layer of TA regulation in bacteria.
摘要：
转录后调控对细菌基因表达的微调起着重要作用。特别是,I型毒素-抗毒素（TA）系统的调节是通过涉及毒素mRNA折叠的复杂机制实现的。这里,我们建立了一种遗传方法来破译幽门螺杆菌中I型TA调控背后的分子基础。我们使用抗毒素染色体失活诱导的致死性来选择抑制毒性的突变。我们发现单点突变足以允许细胞存活。位于毒素的5'非翻译区或开放阅读框内的突变通过稳定隔离Shine-Dalgarno序列的茎环结构来阻碍其翻译。我们建议这些短发夹对应于转录过程中瞬时形成的亚稳态结构，以避免过早的毒素表达。这项工作揭示了翻译的共转录抑制作为细菌中TA调节的附加层。
