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Type III-A CRISPR-Cas Csm Complexes: Assembly, Periodic RNA Cleavage, DNase Activity Regulation, and Autoimmunity
How Type III-A CRISPR-Cas Csm Complexes Form, Cut RNA in Patterns, Control DNA Cutting, and Prevent Self-Attack
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Abstract
Cryo-EM structures reveal 3.1 Å resolution details of the Csm complex involved in RNA targeting.
- Type III CRISPR-Cas systems provide immunity against foreign RNA and DNA through specific RNA degradation mechanisms.
- The structure of the crRNA 5'-repeat tag explains how target cleavage sites are defined using a 5'-ruler mechanism.
- Positions -2 to -5 within the crRNA 5'-repeat act as sensors to prevent autoimmunity.
- Periodic kinks introduced by Csm3 thumb elements in the crRNA-target RNA duplex help achieve cleavage with 6-nucleotide periodicity.
- Autoinhibitory conformations of key Glu residues in Csm1 suggest a regulatory role in DNase activity.
- Mutational studies support insights into the assembly of the Csm complex and the mechanisms of RNA targeting.
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