RNA-activated protein cleavage with a CRISPR-associated endopeptidase.
Science
; 378(6622): 874-881, 2022 11 25.
Article
en 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Endopeptidasas
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Proteínas Bacterianas
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ARN Guía de Kinetoplastida
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Deltaproteobacteria
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Proteolisis
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Proteínas Asociadas a CRISPR
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Sistemas CRISPR-Cas
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos