Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Science. 2014 Apr 18;344(6181):307-10. doi: 10.1126/science.1250897.
Flaviviruses are emerging human pathogens and worldwide health threats. During infection, pathogenic subgenomic flaviviral RNAs (sfRNAs) are produced by resisting degradation by the 5'→3' host cell exonuclease Xrn1 through an unknown RNA structure-based mechanism. Here, we present the crystal structure of a complete Xrn1-resistant flaviviral RNA, which contains interwoven pseudoknots within a compact structure that depends on highly conserved nucleotides. The RNA's three-dimensional topology creates a ringlike conformation, with the 5' end of the resistant structure passing through the ring from one side of the fold to the other. Disruption of this structure prevents formation of sfRNA during flaviviral infection. Thus, sfRNA formation results from an RNA fold that interacts directly with Xrn1, presenting the enzyme with a structure that confounds its helicase activity.
黄病毒是新兴的人类病原体和全球健康威胁。在感染过程中，致病性亚基因组黄病毒 RNA（sfRNA）通过一种未知的基于 RNA 结构的机制抵抗 5'→3'宿主细胞外切酶 Xrn1 的降解而产生。在这里，我们展示了一个完整的 Xrn1 抗性黄病毒 RNA 的晶体结构，该结构包含交织在紧凑结构内的假结，这取决于高度保守的核苷酸。该 RNA 的三维拓扑结构创建了一个环状构象，抗性结构的 5'端从折叠的一侧穿过环到另一侧。破坏这种结构可防止 sfRNA 在黄病毒感染期间形成。因此，sfRNA 的形成是由于与 Xrn1 直接相互作用的 RNA 折叠，向酶呈现一种使其解旋酶活性受到干扰的结构。
