The carbon storage regulator system and base-pairing small RNAs (sRNAs) represent two predominant modes of bacterial post-transcriptional regulation, which globally influence gene expression. Binding of CsrA protein to the 5′ UTR or initial mRNA coding sequences can affect translation, RNA stability, and/or transcript elongation. Base-pairing sRNAs also regulate these processes, often requiring assistance from the RNA chaperone Hfq. Transcriptomics studies in Escherichia coli have identified many new CsrA targets, including Spot 42 and other base-pairing sRNAs. Spot 42 synthesis is repressed by cAMP-CRP, induced by the presence of glucose, and Spot 42 post-transcriptionally represses operons that facilitate metabolism of nonpreferred carbon sources. CsrA activity is also increased by glucose via effects on CsrA sRNA antagonists, CsrB/C. Here, we elucidate a mechanism wherein CsrA binds to and protects Spot 42 sRNA from RNase E-mediated cleavage. This protection leads to enhanced repression of srlA by Spot 42, a gene required for sorbitol uptake. A second, independent mechanism by which CsrA represses srlA is by binding to and inhibiting translation of srlM mRNA, encoding a transcriptional activator of srlA. Our findings demonstrate a novel means of regulation, by CsrA binding to a sRNA, and indicate that such interactions can help to shape complex bacterial regulatory circuitry.

中文翻译：

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通过结合碱基配对小 RNA Spot 42 进行 CsrA 调节

碳储存调节系统和碱基配对小 RNA (sRNA) 代表细菌转录后调控的两种主要模式，它们在全球范围内影响基因表达。CsrA 蛋白与 5' UTR 或初始 mRNA 编码序列的结合可影响翻译、RNA 稳定性和/或转录物延伸。碱基配对 sRNA 也调节这些过程，通常需要 RNA 伴侣 Hfq 的帮助。大肠杆菌的转录组学研究已经确定了许多新的 CsrA 目标，包括 Spot 42 和其他碱基配对 sRNA。Spot 42 合成被 cAMP-CRP 抑制，由葡萄糖的存在诱导，Spot 42 转录后抑制促进非首选碳源代谢的操纵子。葡萄糖通过对 CsrA sRNA 拮抗剂 CsrB/C 的影响也增加了 CsrA 活性。在这里，我们阐明了一种机制，其中 CsrA 结合并保护 Spot 42 sRNA 免受 RNase E 介导的切割。这种保护导致Spot 42 对srlA的抑制增强，Spot 42 是摄取山梨糖醇所需的基因。CsrA 抑制srlA的第二个独立机制是通过结合并抑制srlM mRNA 的翻译，编码srlA的转录激活因子. 我们的研究结果展示了一种新的调节方式，即 CsrA 与 sRNA 的结合，并表明这种相互作用有助于形成复杂的细菌调节回路。