Sefcikova Jana, Roth Mitchell, Yu Ge, Li Hong
Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, USA.
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA.
Bioessays. 2017 Jun;39(6). doi: 10.1002/bies.201700019. Epub 2017 May 11.
RNA molecules are flexible yet foldable. Proteins must cope with this structural duality when forming biologically active complexes with RNA. Recent studies of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs)-mediated RNA immunity illustrate some remarkable mechanisms with which proteins interact with RNA. Currently known structures of CRISPR-Cas6 endoribonucleases bound with RNA suggest a conserved protein recognition mechanism mediated by RNA stem-loops. However, a survey of CRISPR RNA reveals that many repeats either lack a productive stem-loop (Relaxed) or possess stable but inhibitory structures (Tight), which raises the question of how the enzyme processes structurally diverse RNA. In reviewing recent literature, we propose a bivalent trapping and an unwinding mechanism for CRISPR-Cas6 to interact with the Relaxed and the Tight repeat RNA, respectively. Both mechanisms aim to create an identical RNA conformation at the cleavage site for accurate processing.
RNA分子具有柔韧性但也可折叠。蛋白质在与RNA形成生物活性复合物时必须应对这种结构上的双重性。近期对成簇规律间隔短回文重复序列（CRISPRs）介导的RNA免疫的研究阐明了蛋白质与RNA相互作用的一些显著机制。目前已知的与RNA结合的CRISPR-Cas6核糖核酸内切酶结构表明存在一种由RNA茎环介导的保守蛋白质识别机制。然而，对CRISPR RNA的一项调查显示，许多重复序列要么缺乏有效的茎环（松弛型），要么具有稳定但有抑制作用的结构（紧密型），这就提出了该酶如何处理结构多样的RNA的问题。在回顾近期文献时，我们提出了一种二价捕获机制和一种解旋机制，分别用于CRISPR-Cas6与松弛型和紧密型重复RNA相互作用。这两种机制的目的都是在切割位点产生相同的RNA构象，以便进行精确加工。
