Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors

Basem Al-Shayeb, Petr Skopintsev, Katarzyna M. Soczek, Elizabeth C. Stahl, Zheng Li, Evan Groover, Dylan Smock, Amy R. Eggers, Patrick Pausch, Brady F. Cress, Carolyn J. Huang, Brian Staskawicz, David F. Savage, Steven E. Jacobsen, Jillian F. Banfield, Jennifer A. Doudna

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

CRISPR-Cas systems are host-encoded pathways that protect microbes from viral infection using an adaptive RNA-guided mechanism. Using genome-resolved metagenomics, we find that CRISPR systems are also encoded in diverse bacteriophages, where they occur as divergent and hypercompact anti-viral systems. Bacteriophage-encoded CRISPR systems belong to all six known CRISPR-Cas types, though some lack crucial components, suggesting alternate functional roles or host complementation. We describe multiple new Cas9-like proteins and 44 families related to type V CRISPR-Cas systems, including the Casλ RNA-guided nuclease family. Among the most divergent of the new enzymes identified, Casλ recognizes double-stranded DNA using a uniquely structured CRISPR RNA (crRNA). The Casλ-RNA-DNA structure determined by cryoelectron microscopy reveals a compact bilobed architecture capable of inducing genome editing in mammalian, Arabidopsis, and hexaploid wheat cells. These findings reveal a new source of CRISPR-Cas enzymes in phages and highlight their value as genome editors in plant and human cells.

Original languageEnglish
Pages (from-to)4574-4586.e16
Number of pages30
JournalCell
Volume185
Issue number24
DOIs
Publication statusPublished - 23 Nov 2022
Externally publishedYes

Keywords

  • anti-viral
  • CRISPR
  • CRISPR-Cas
  • enzyme
  • genome editing
  • genome editor
  • metagenomics
  • phage
  • structure
  • tool

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