Structures and mechanisms of CRISPR RNA-guided effector nucleases
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Updated: Mar 11, 2026

Substrate Generation for Endonucleases of CRISPR/Cas Systems
Published on: September 8, 2012
Hiroshi Nishimasu1, Osamu Nureki2
1Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; JST, PRESTO, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Abstract:
In the prokaryotic CRISPR-Cas adaptive immune systems, a CRISPR RNA (crRNA) assembles with multiple or single Cas proteins to form crRNA ribonucleoprotein (crRNP) effector complexes, responsible for the destruction of invading genetic elements. Although the mechanisms of target recognition and cleavage by the crRNP effectors are quite diverse among the different types of CRISPR-Cas systems, the basic action principles of these crRNA-guided effector nucleases are highly conserved. In all of the crRNP effectors, the repeat-derived invariant and spacer-derived variable segments of the crRNA are recognized by the Cas protein(s) in sequence-dependent and sequence-independent manners, respectively, with the spacer-derived guide segment available for base pairing with target nucleic acids. Over the past few years, intensive studies have provided an atomic view of the crRNA-guided target interference mechanisms in different types of CRISPR-Cas systems. Here, we review the recent progress toward structural and mechanistic understanding of the diverse crRNP effector nucleases.
Insights
CRISPR-Cas systems use crRNA-guided effector complexes (crRNPs) to destroy invading DNA. Recent structural studies reveal conserved mechanisms for target recognition and cleavage across diverse CRISPR-Cas nucleases.
Area of Science:
- Microbiology
- Molecular Biology
- Biochemistry
Background:
- Prokaryotic CRISPR-Cas systems provide adaptive immunity against genetic elements.
- CRISPR RNA (crRNA) assembles with Cas proteins into crRNA ribonucleoprotein (crRNP) effector complexes.
- These crRNPs are responsible for recognizing and destroying foreign nucleic acids.
Purpose of the Study:
- To review recent progress in understanding the structure and mechanisms of diverse crRNP effector nucleases.
- To highlight conserved principles in crRNA-guided target interference.
- To provide an atomic view of CRISPR-Cas interference mechanisms.
Main Methods:
- Review of recent structural and mechanistic studies on CRISPR-Cas systems.
- Analysis of diverse crRNP effector complexes.
- Focus on atomic-level insights into target recognition and cleavage.
Main Results:
- CRISPR-Cas effector mechanisms, while diverse, share conserved basic action principles.
- crRNA segments (repeat-derived and spacer-derived) are recognized by Cas proteins.
- Spacer-derived segments guide target binding via base pairing.
Conclusions:
- Intensive research has provided atomic-level understanding of crRNA-guided target interference.
- Diverse CRISPR-Cas nucleases operate via conserved crRNA-guided mechanisms.
- Structural and mechanistic insights continue to advance the field of CRISPR-Cas biology.
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