RNA-activated protein cleavage with a CRISPR-associated endopeptidase.
Science
; 378(6622): 874-881, 2022 11 25.
Article
in En
| MEDLINE
| ID: mdl-36423276
ABSTRACT
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 Desulfonema ishimotonii 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endopeptidases
/
Bacterial Proteins
/
RNA, Guide, Kinetoplastida
/
Deltaproteobacteria
/
Proteolysis
/
CRISPR-Associated Proteins
/
CRISPR-Cas Systems
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Science
Year:
2022
Document type:
Article
Affiliation country:
United States