Exoribonuclease-resistant RNAs (xrRNAs) from viruses prevent digestion by host exoribonucleases, creating sub-genomic viral RNAs that can enhance infection and pathogenicity. Novel knotted structures in xrRNAs are proposed to act as mechanical roadblocks to RNases. Studying an xrRNA from Zika virus with optical tweezers, we found that it was the most mechanically stable RNA structure yet observed. The knot folded by threading the 5′ end into the cleft of a Mg2+-coordinated three-helix junction before pseudoknot interactions closed a ring around it. Both the threading and pseudoknot were required to generate the extremely force-resistant knot, whose formation correlated directly with RNase resistance both in the wild-type xrRNA and a low-resistance mutant. This work clarifies the folding and mechanism of action of an important new class of RNA.

中文翻译：

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Zika病毒RNA中通过链穿线形成的机械稳定结赋予RNase抗性

病毒产生的抗外切核糖核酸酶的RNA（xrRNA）阻止了宿主外切核糖核酸酶的消化，形成了亚基因组病毒RNA，可以增强感染和致病性。提出了xrRNA中的新型打结结构，可充当RNase的机械障碍。用光镊研究Zika病毒的xrRNA，我们发现它是迄今观察到的最机械稳定的RNA结构。通过在假结相互作用封闭其周围的环之前将5'端旋入Mg2 +配位的三螺旋结的缝隙中而折叠结。穿线和假结都需要产生极强的抗力结，其形成与野生型xrRNA和低抗性突变体中的RNase抗性直接相关。这项工作阐明了重要的一类新的RNA的折叠和作用机理。