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

Cell

Innovative Genomics Institute, University of California, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA, USA; Department of Chemistry, University of California, Berkeley, CA, USA; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Gladstone Institutes, University of California, San Francisco, CA, USA. Electronic address:

Published: November 2022

CRISPR-Cas systems are mechanisms in microbes that protect against viral infections using adaptive RNA guidance, and researchers discovered these systems also exist in various bacteriophages.
Bacteriophage-encoded CRISPR systems include all six known types but some are missing key components, indicating they might serve different functions or rely on hosts for support.
The study introduces new Cas9-like proteins and the Casλ family, which has a unique structure for recognizing DNA and has shown potential for genome editing in plants and animals, emphasizing the importance of phage-derived CRISPR-Cas enzymes.

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.

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http://dx.doi.org/10.1016/j.cell.2022.10.020	DOI Listing

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