Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella
Small RNA-based feedforward loop with AND-gate logic regulates extrachromosomal DNA transfer in Salmonella
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DOI：
10.1073/pnas.1507825112
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发表时间：
2015-08-25
影响因子：
11.1
通讯作者：
Vogel, Joerg
中科院分区：
文献类型：
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作者：
Papenfort, Kai;Espinosa, Elena;Vogel, Joerg
通过质粒偶联的水平基因转移是微生物进化的主要驱动力，但这是一个复杂的过程，需要与宿主细菌的生理状态同步。虽然已知有几种宿主转录因子调节质粒携带的转移基因，但基于rna的宿主-质粒通讯调节回路仍然未知。我们描述了一种转录后机制，即hfq依赖性小RNA RprA抑制肠沙门氏菌毒力质粒pSLT的转移。RprA使用两个独立的种子配对结构域来激活sigma因子sigma(S)和RicI蛋白的mrna， RicI蛋白是一种以前未被表征的膜蛋白，在这里显示出抑制结合。ricI的转录需要sigma(S)， RprA和sigma(S)共同协调一个具有and门逻辑的前馈循环，以严格控制ricI合成的激活。RicI与偶联器蛋白TraV相互作用，在膜损伤条件下限制质粒转移。据我们所知，本研究报道了第一个依赖于两个独立靶点转录后激活的小RNA控制的前馈环，以及保守的RprA小RNA在控制染色体外DNA转移中的意想不到的作用。
Horizontal gene transfer via plasmid conjugation is a major driving force in microbial evolution but constitutes a complex process that requires synchronization with the physiological state of the host bacteria. Although several host transcription factors are known to regulate plasmid-borne transfer genes, RNA-based regulatory circuits for host-plasmid communication remain unknown. We describe a posttranscriptional mechanism whereby the Hfq-dependent small RNA, RprA, inhibits transfer of pSLT, the virulence plasmid of Salmonella enterica. RprA employs two separate seed-pairing domains to activate the mRNAs of both the sigma-factor sigma(S) and the RicI protein, a previously uncharacterized membrane protein here shown to inhibit conjugation. Transcription of ricI requires sigma(S) and, together, RprA and sigma(S) orchestrate a coherent feedforward loop with AND-gate logic to tightly control the activation of RicI synthesis. RicI interacts with the conjugation apparatus protein TraV and limits plasmid transfer under membrane-damaging conditions. To our knowledge, this study reports the first small RNA-controlled feedforward loop relying on posttranscriptional activation of two independent targets and an unexpected role of the conserved RprA small RNA in controlling extrachromosomal DNA transfer.