Department of Microbiology and Cell Science, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611.
Department of Biochemistry and Molecular Biology.
Microbiol Spectr. 2018 Mar;6(2). doi: 10.1128/microbiolspec.RWR-0009-2017.
The sequence-specific RNA binding protein CsrA is employed by diverse bacteria in the posttranscriptional regulation of gene expression. Its binding interactions with RNA have been documented at atomic resolution and shown to alter RNA secondary structure, RNA stability, translation, and/or Rho-mediated transcription termination through a growing number of molecular mechanisms. In , small regulatory RNAs (sRNAs) that contain multiple CsrA binding sites compete with mRNA for binding to CsrA, thereby sequestering and antagonizing this protein. Both the synthesis and turnover of these sRNAs are regulated, allowing CsrA activity to be rapidly and efficiently adjusted in response to nutritional conditions and stresses. Feedback loops between the Csr regulatory components improve the dynamics of signal response by the Csr system. The Csr system of is intimately interconnected with other global regulatory systems, permitting it to contribute to regulation by those systems. In some species, a protein antagonist of CsrA functions as part of a checkpoint for flagellum biosynthesis. In other species, a protein antagonist participates in a mechanism in which a type III secretion system is used for sensing interactions with host cells. Recent transcriptomics studies reveal vast effects of CsrA on gene expression through direct binding to hundreds of mRNAs, and indirectly through its effects on the expression of dozens of transcription factors. CsrA binding to base-pairing sRNAs and novel mRNA segments, such as the 3' untranslated region and deep within coding regions, predict its participation in yet-to-be-discovered regulatory mechanisms.
序列特异性 RNA 结合蛋白 CsrA 被多种细菌用于基因表达的转录后调控。其与 RNA 的结合相互作用已在原子分辨率水平得到证实，并通过越来越多的分子机制显示出改变 RNA 二级结构、RNA 稳定性、翻译和/或 Rho 介导的转录终止的能力。在 中，含有多个 CsrA 结合位点的小调控 RNA（sRNA）与 mRNA 竞争与 CsrA 的结合，从而将其隔离并拮抗这种蛋白质。这些 sRNA 的合成和周转都受到调控，使得 CsrA 的活性可以根据营养条件和应激迅速有效地进行调整。Csr 调节成分之间的反馈回路通过 Csr 系统提高了信号响应的动力学。 的 Csr 系统与其他全局调节系统密切相关，使其能够为这些系统的调节做出贡献。在一些物种中，CsrA 的蛋白拮抗剂作为鞭毛生物合成的检查点的一部分发挥作用。在其他物种中，蛋白拮抗剂参与一种机制，其中 III 型分泌系统用于感知与宿主细胞的相互作用。最近的转录组学研究揭示了 CsrA 通过直接与数百个 mRNA 结合以及通过对数十个转录因子表达的间接影响对基因表达产生广泛影响。CsrA 与碱基配对 sRNA 和新型 mRNA 片段（如 3'非翻译区和编码区内部深处）的结合，预测了其参与尚未发现的调节机制。
