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Science· 2026Q1

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

Peter H. Yoon, Kenneth J. Loi, Zeyuan Terry Zhang, Trevor A. Docter et al.

Short summary

Researchers discovered Viral Interference Programmable Repeat (VIPR) systems, an ancient precursor to CRISPR-Cas, which use a noncontiguous RNA code to recognize DNA targets, unlike modern CRISPR systems.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Discovery of VIPR systems, an ancestral RNA-guided DNA recognition system.
  • vrRNAs use a noncontiguous code with variable NN dinucleotides to specify gapped DNA targets.
  • VIPR systems likely defended against competing phages in ancient viral warfare.
  • Programmable phage defense demonstrated by redirecting the VIPR complex for transcriptional repression.

AI-generated from the title and abstract; the full text is not read.

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.

The authors' abstract, as published at the source. Science, 2026 · DOI ↗

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Field: Molecular Biology

Molecular BiologyBiochemistry, Genetics and Molecular Biology