2026年9月17日，美国加州大学伯克利分校Peter H. Yoon等科学家在《科学》（Science）发表研究，发现了CRISPR-Cas起源处RNA引导DNA识别的非连续代码。

CRISPR-Cas提供RNA介导的适应性免疫，但其第一个RNA引导效应器如何出现尚不清楚。在这项研究中，研究人员报道了病毒干扰可编程重复（VIPR）系统的发现，该系统由一种作为最早CRISPR-Cas效应器祖先的Vipr蛋白和由交替GGY/NN基序组成的VIPR RNA（vrRNA）构成。与通过连续互补与靶核酸配对的标准向导RNA不同，vrRNA通过一种非连续代码识别双链DNA，其中可变的NN二核苷酸共同指定一个带缺口的靶序列。天然的vrRNA靶标表明VIPR系统作用于对抗竞争性噬菌体，并且研究人员通过重新定向该复合物进行转录抑制，展示了可编程的噬菌体防御。这些结果表明，适应性免疫起源于病毒之间的古老战争，揭示了一种此前未被识别的序列信息编码逻辑。

附：英文原文

Title: A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas

Author: Peter H. Yoon, Kenneth J. Loi, Zeyuan Terry Zhang, Trevor A. Docter, Santiago C. Lopez, Conner J. Langeberg, Muhammad Moez Ur-Rehman, Kamakshi Vohra, Zehan Zhou, Isabel Esain-Garcia, Marena I. Trinidad, Honglue Shi, Ron Boger, Peter Y. Wang, Benjamin A. Adler, Stephen G. Brohawn, Jennifer A. Doudna

Issue&Volume: 2026-09-17

Abstract: CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors and VIPR RNAs (vrRNAs) comprising alternating GGY/NN motifs. Unlike canonical guide RNAs that pair with target nucleic acids through contiguous complementarity, vrRNAs recognize double-stranded DNA through a noncontiguous code in which the variable NN dinucleotides collectively specify a gapped target sequence. Natural vrRNA targets suggest that VIPR systems act against competing phages, and we demonstrate programmable phage defense by redirecting the complex for transcriptional repression. These results suggest that adaptive immunity originated from ancient warfare between viruses, revealing a previously unidentified logic for encoding information in sequence.

DOI: 10.1126/science.aei0498

Source: https://www.science.org/doi/10.1126/science.aei0498