Programmable RNA targeting with the single-protein CRISPR effector Cas7-11
- PMID:34489594
- DOI: 10.1038/s41586-021-03886-5
Programmable RNA targeting with the single-protein CRISPR effector Cas7-11
Erratum in
- Author Correction: Programmable RNA targeting with the single-protein CRISPR effector Cas7-11.Özcan A, Krajeski R, Ioannidi E, Lee B, Gardner A, Makarova KS, Koonin EV, Abudayyeh OO, Gootenberg JS.Özcan A, et al.Nature. 2022 Aug;608(7923):E30. doi: 10.1038/s41586-022-05003-6.Nature. 2022.PMID:35896753No abstract available.
Abstract
CRISPR-Cas interference is mediated by Cas effector nucleases that are either components of multisubunit complexes-in class 1 CRISPR-Cas systems-or domains of a single protein-in class 2 systems1-3. Here we show that the subtype III-E effector Cas7-11 is a single-protein effector in the class 1 CRISPR-Cas systems originating from the fusion of a putative Cas11 domain and multiple Cas7 subunits that are derived from subtype III-D. Cas7-11 from Desulfonema ishimotonii (DiCas7-11), when expressed in Escherichia coli, has substantial RNA interference effectivity against mRNAs and bacteriophages. Similar to many class 2 effectors-and unique among class 1 systems-DiCas7-11 processes pre-CRISPR RNA into mature CRISPR RNA (crRNA) and cleaves RNA at positions defined by the target:spacer duplex, without detectable non-specific activity. We engineered Cas7-11 for RNA knockdown and editing in mammalian cells. We show that Cas7-11 has no effects on cell viability, whereas other RNA-targeting tools (such as short hairpin RNAs and Cas13) show substantial cell toxicity4,5. This study illustrates the evolution of a single-protein effector from multisubunit class 1 effector complexes, expanding our understanding of the diversity of CRISPR systems. Cas7-11 provides the basis for new programmable RNA-targeting tools that are free of collateral activity and cell toxicity.
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
Comment in
- Expanding RNA target effectors.Tang L.Tang L.Nat Methods. 2021 Nov;18(11):1276. doi: 10.1038/s41592-021-01323-z.Nat Methods. 2021.PMID:34732901No abstract available.
- New Type III CRISPR variant and programmable RNA targeting tool: Oh, thank heaven for Cas7-11.Catchpole RJ, Terns MP.Catchpole RJ, et al.Mol Cell. 2021 Nov 4;81(21):4354-4356. doi: 10.1016/j.molcel.2021.10.014.Mol Cell. 2021.PMID:34739827Free PMC article.
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References
- Wang, Q. et al. The CRISPR–Cas13a gene‐editing system induces collateral cleavage of RNA in glioma cells. Adv. Sci. 1, 1901299 (2019). - DOI
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