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Paradigm Challenge  /  Biology

CRISPR-Cas complexes are not actually protein scissors, but machines where the RNA itself performs the cutting.

CRISPR technology is usually explained as a protein sculptor that uses an RNA guide to find a target and snip it. This research shows that in Type III systems, the protein is just a helper that holds everything in place. The actual chemical work of cutting the target is done by the RNA molecule itself acting as a ribozyme. This discovery fundamentally changes our understanding of the origins of the immune system in bacteria. It allows engineers to build more precise gene-editing tools by focusing on the RNA's own catalytic power.

Original Paper

Type III CRISPR-Cas effectors act as protein-assisted ribozymes during RNA cleavage

David Taylor, Evan Schwartz, Jack Bravo, Mohd Ahsan, Luis Macias, Caitlyn McCafferty, Tyler Dangerfield, Jada Walker, Jennifer Brodbelt, Giulia Palermo, Peter Fineran, Robert Fagerlund

research_square  ·  rs-2837968

Abstract CRISPR-Cas systems are an adaptive immune system in bacteria and archaea that utilize CRISPR RNA-guided surveillance complexes to target complementary RNA or DNA for destruction. Target RNA cleavage at regular intervals is characteristic of type III effector complexes; however, the mechanism has remained enigmatic. Here, we determine the structures of the Synechocystis type III-Dv complex, an evolutionary intermediate in type III effectors, in pre- and post-cleavage states, which show m