2026年9月17日，美国加州大学伯克利分校Trevor A. Docter等科学家在《科学》（Science）发表研究，揭示了VIPR RNA通过非连续几何三链形成引导DNA识别的机制。

病毒干扰可编程重复（VIPR）系统使用一种非连续代码进行RNA引导的转录沉默。Vipr蛋白和由交替GGY与NN片段组成的VIPR RNA（vrRNA）如何实现精确的DNA靶向尚不清楚。在此，研究人员展示了21个冷冻电镜结构，有助于解释靶标接合机制。Vipr原聚体沿vrRNA寡聚化，形成右手螺旋丝，隔离每个GGY基序，并将相邻的NN碱基定位以进行靶碱基配对。DNA结合时每隔三个核苷酸跳跃一次，产生一个带缺口的vrRNA-DNA杂交螺旋，该螺旋环绕非靶DNA链，形成几何三链。这些发现表明，三链介导的靶链交接可能使VIPR系统中实现非连续且可编程的RNA引导DNA识别。

附：英文原文

Title: VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation

Author: Peter H. Yoon, Trevor A. Docter, Zeyuan Terry Zhang, Kenneth Loi, Santiago C. Lopez, Luis E. Valentin-Alvarado, Owen T. Tuck, Stephen G. Brohawn, Jennifer A. Doudna

Issue&Volume: 2026-09-17

Abstract: Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo–electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.

DOI: 10.1126/science.aei3472

Source: https://www.science.org/doi/10.1126/science.aei3472