ArticleCell host & microbe2022
A target expression threshold dictates invader defense and prevents autoimmunity by CRISPR-Cas13.
Article in Cell host & microbe, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Conditional activation of Cas13 enforces lysogeny in a native type VI-A CRISPR host.Nature microbiology · 2026Article
- The complexity of multiple CRISPR arrays in strains with (co-occurring) CRISPR systems.microLife · 2026Article
- Article
- Argonaute-HNH filaments triggered by invader DNA confer bacterial immunity.Nature communications · 2025Article
- Crosstalk between three CRISPR-Cas types enables primed type VI-A adaptation in Listeria seeligeri.Cell host & microbe · 2025Article
- An archaeal chronic virus escapes the immunity of prokaryotic Argonaute.Nucleic acids research · 2025Article
- Principles of CRISPR-Cas13 mismatch intolerance enable selective silencing of point-mutated oncogenic RNA with single-base precision.Science advances · 2024Article
- The rise and future of CRISPR-based approaches for high-throughput genomics.FEMS microbiology reviews · 2024Review
- Prokaryotic Argonaute nuclease cooperates with co-encoded RNase to acquire guide RNAs and target invader DNA.Nucleic acids research · 2024Article
- Systematic interrogation of CRISPR antimicrobials in Klebsiella pneumoniae reveals nuclease-, guide- and strain-dependent features influencing antimicrobial activity.Nucleic acids research · 2024Article
- DNA-targeting short Argonautes complex with effector proteins for collateral nuclease activity and bacterial population immunity.Nature microbiology · 2024Article
- Improved prediction of bacterial CRISPRi guide efficiency from depletion screens through mixed-effect machine learning and data integration.Genome biology · 2024Article
- Genetic manipulation of bacteriophage T4 utilizing the CRISPR-Cas13b system.Frontiers in genome editing · 2024Article
- Csx28 is a membrane pore that enhances CRISPR-Cas13b-dependent antiphage defense.Science (New York, N.Y.) · 2023Article
- Systematically attenuating DNA targeting enables CRISPR-driven editing in bacteria.Nature communications · 2023Article
- The collateral activity of RfxCas13d can induce lethality in a RfxCas13d knock-in mouse model.Genome biology · 2023Article
- Optimization of specific RNA knockdown in mammalian cells with CRISPR-Cas13.Methods (San Diego, Calif.) · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
CRISPR-Cas systems must enact robust immunity against foreign genetic material without inducing cytotoxic autoimmunity. For type VI systems that use Cas13 nucleases and recognize RNA targets, immune activation requires extensive CRISPR RNA (crRNA) guide-target complementarity and a target-flanking motif. Here, we report a third requirement shaping the immune response: the expression of the target transcript exceeding a threshold. We found that endogenous non-essential transcripts targeted by crRNAs rarely elicited autoimmunity. Instead, autoimmune induction required over-expressing the targeted transcripts above a threshold. A genome-wide screen confirmed target expression levels as a global determinant of cytotoxic autoimmunity and revealed that this threshold shifts with each guide-target pair. This threshold further ensured defense against a lytic bacteriophage yet allowed the tolerance of a targeted beneficial gene expressed from an invading plasmid. These findings establish target expression levels as an additional criterion for immune defense by RNA-targeting CRISPR-Cas systems, preventing autoimmunity and distinguishing pathogenic and benign invaders.
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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.