The gRAMP CRISPR-Cas effector is an RNA endonuclease complexed with a caspase-like peptidase

Abstract

Description CRISPR and Caspase meet Many prokaryotes use CRISPR RNA–bound proteins to sense viral RNA instead of DNA to set an immune response in motion that protects from virus infection. Although these ribonucleoproteins are typically composed of many protein subunits, van Beljouw et al. discovered that CRISPR-Cas type III-E systems are formed by a large, single-component effector protein capable of double RNA cleavage. Distinct from other systems, this effector forms a complex with a peptidase from the caspase family, raising the intriguing possibility that viral RNA activates a protease activity to prevent virus propagation by host suicide. —DJ A single subunit type III-E effector cleaves RNA at two guide-defined positions and associates with a caspase-like peptidase. Type III CRISPR-Cas immunity is widespread in prokaryotes and is generally mediated by multisubunit effector complexes. These complexes recognize complementary viral transcripts and can activate ancillary immune proteins. Here, we describe a type III-E effector from Candidatus “Scalindua brodae” (Sb-gRAMP), which is natively encoded by a single gene with several type III domains fused together. This effector uses CRISPR RNA to guide target RNA recognition and cleaves single-stranded RNA at two defined positions six nucleotides apart. Sb-gRAMP physically combines with the caspase-like TPR-CHAT peptidase to form the CRISPR-guided caspase (Craspase) complex, suggesting a potential mechanism of target RNA–induced protease activity to gain viral immunity.