National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)
1DP1-HL141201
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
2R01HG009761-05
米国
引用
ジャーナル: Science / 年: 2022 タイトル: RNA-activated protein cleavage with a CRISPR-associated endopeptidase. 著者: Jonathan Strecker / F Esra Demircioglu / David Li / Guilhem Faure / Max E Wilkinson / Jonathan S Gootenberg / Omar O Abudayyeh / Hiroshi Nishimasu / Rhiannon K Macrae / Feng Zhang / 要旨: In prokaryotes, CRISPR-Cas systems provide adaptive immune responses against foreign genetic elements through RNA-guided nuclease activity. Recently, additional genes with non-nuclease functions have ...In prokaryotes, CRISPR-Cas systems provide adaptive immune responses against foreign genetic elements through RNA-guided nuclease activity. Recently, additional genes with non-nuclease functions have been found in genetic association with CRISPR systems, suggesting that there may be other RNA-guided non-nucleolytic enzymes. One such gene from encodes the TPR-CHAT protease Csx29, which is associated with the CRISPR effector Cas7-11. Here, we demonstrate that this CRISPR-associated protease (CASP) exhibits programmable RNA-activated endopeptidase activity against a sigma factor inhibitor to regulate a transcriptional response. Cryo-electron microscopy of an active and substrate-bound CASP complex reveals an allosteric activation mechanism that reorganizes Csx29 catalytic residues upon target RNA binding. This work reveals an RNA-guided function in nature that can be leveraged for RNA-sensing applications in vitro and in human cells.