van Nues Rob W, Castro-Roa Daniel, Yuzenkova Yulia, Zenkin Nikolay
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK.
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4AX, UK
Nucleic Acids Res. 2016 Apr 7;44(6):2577-92. doi: 10.1093/nar/gkv1302. Epub 2015 Nov 24.
Coupled transcription and translation in bacteria are tightly regulated. Some small RNAs (sRNAs) control aspects of this coupling by modifying ribosome access or inducing degradation of the message. Here, we show that sRNA IsrA (IS61 or McaS) specifically associates with core enzyme of RNAP in vivo and in vitro, independently of σ factor and away from the main nucleic-acids-binding channel of RNAP. We also show that, in the cells, IsrA exists as ribonucleoprotein particles (sRNPs), which involve a defined set of proteins including Hfq, S1, CsrA, ProQ and PNPase. Our findings suggest that IsrA might be directly involved in transcription or can participate in regulation of gene expression by delivering proteins associated with it to target mRNAs through its interactions with transcribing RNAP and through regions of sequence-complementarity with the target. In this eukaryotic-like model only in the context of a complex with its target, IsrA and its associated proteins become active. In this manner, in the form of sRNPs, bacterial sRNAs could regulate a number of targets with various outcomes, depending on the set of associated proteins.
细菌中的转录与翻译偶联受到严格调控。一些小RNA(sRNA)通过改变核糖体的可及性或诱导信使RNA降解来控制这种偶联的某些方面。在此,我们表明sRNA IsrA(IS61或McaS)在体内和体外均能特异性地与RNA聚合酶(RNAP)的核心酶结合,这种结合不依赖于σ因子,且远离RNAP的主要核酸结合通道。我们还表明,在细胞中,IsrA以核糖核蛋白颗粒(sRNP)的形式存在,这些颗粒包含一组特定的蛋白质,包括Hfq、S1、CsrA、ProQ和PNPase。我们的研究结果表明,IsrA可能直接参与转录过程,或者通过与正在转录的RNAP相互作用以及与靶标mRNA的序列互补区域,将与其相关的蛋白质传递给靶标mRNA,从而参与基因表达的调控。在这种类似真核生物的模式中,只有在与其靶标形成复合物的情况下,IsrA及其相关蛋白质才会变得活跃。通过这种方式,以sRNP的形式,细菌sRNA可以根据相关蛋白质的组合来调控多个靶标,并产生不同的结果。