ArticleNature microbiology2022
Spacer prioritization in CRISPR-Cas9 immunity is enabled by the leader RNA.
Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- A leader-repeat hairpin blocks extraneous CRISPR RNA production in diverse CRISPR-Cas13 systems.The EMBO journal · 2026Article
- The complexity of multiple CRISPR arrays in strains with (co-occurring) CRISPR systems.microLife · 2026Article
- Genetic Engineering and Encapsulation Strategies forFoods (Basel, Switzerland) · 2026Review
- Comprehensive analysis of CRISPR array repeat mutations reveals subtype-specific patterns and links to spacer dynamics.microLife · 2026Article
- AnMicroorganisms · 2025Article
- Article
- Discovery of Diverse CRISPR Leader Motifs, Putative Functions, and Applications for Enhanced CRISPR Detection and Subtype Annotation.The CRISPR journal · 2025Article
- Disparate mechanisms counteract extraneous CRISPR RNA production in type II-C CRISPR-Cas systems.microLife · 2025Article
- The intricate pathogenicity of Group AVirulence · 2024Review
- A dynamic subpopulation of CRISPR-Cas overexpressers allows Streptococcus pyogenes to rapidly respond to phage.Nature microbiology · 2024Article
- Isoform-specific RNA structure determination using Nano-DMS-MaP.Nature protocols · 2024Review
- Application and progress of CRISPR/Cas9 gene editing in B-cell lymphoma: a narrative review.Translational cancer research · 2024Review
- Structure reveals why genome folding is necessary for site-specific integration of foreign DNA into CRISPR arrays.Nature structural & molecular biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
CRISPR-Cas systems store fragments of foreign DNA, called spacers, as immunological recordings used to combat future infections. Of the many spacers stored in a CRISPR array, the most recent are known to be prioritized for immune defence. However, the underlying mechanism remains unclear. Here we show that the leader region upstream of CRISPR arrays in CRISPR-Cas9 systems enhances CRISPR RNA (crRNA) processing from the newest spacer, prioritizing defence against the matching invader. Using the CRISPR-Cas9 system from Streptococcus pyogenes as a model, we found that the transcribed leader interacts with the conserved repeats bordering the newest spacer. The resulting interaction promotes transactivating crRNA (tracrRNA) hybridization with the second of the two repeats, accelerating crRNA processing. Accordingly, disruption of this structure reduces the abundance of the associated crRNA and immune defence against targeted plasmids and bacteriophages. Beyond the S. pyogenes system, bioinformatics analyses revealed that leader-repeat structures appear across CRISPR-Cas9 systems. CRISPR-Cas systems thus possess an RNA-based mechanism to prioritize defence against the most recently encountered invaders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.