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

VIRAL INTERFERENCE PROGRAMMABLE REPEAT (VIPR) SYSTEMS WITH NONCONTIGUOUS DNA RECOGNITION SUGGEST ORIGIN OF CRISPR-CAS IMMUNITY

• Why it matters: Understanding how RNA-guided effectors first arose is crucial for revealing the evolution of adaptive immunity in microbes. This work addresses the gap by exploring ancestral systems that predate canonical CRISPR-Cas effectors.
• What they did: The study identified VIPR systems consisting of a Vipr protein and vrRNAs with alternating GGY/NN motifs, which recognize DNA through a noncontiguous code involving gapped target sequences, and demonstrated programmable phage defense.
• The result: Findings imply that ancient viral warfare shaped the origin of adaptive immunity and reveal a new logic for encoding information in sequence, enabling potential transcriptional repression-based phage defense.