ArticleNucleic acids research2024
Molecular mechanism for target RNA recognition and cleavage of Cas13h.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Cas13d-Mediated Knockdown of Long Noncoding RNAs.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Beyond DNA editing: how Cas13 redefined programmable RNA manipulation and what still limits its therapeutic promise.Nucleic acids research · 2026Review
- Mechanistic insights into Cas13d enzymes from cryo-EM structures of CasRx and DjCas13d.Nucleic acids research · 2025Article
- Recent advances in CRISPR-based single-nucleotide fidelity diagnostics.Communications medicine · 2025Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
RNA-targeting type VI CRISPR-Cas effectors are widely used in RNA applications. Cas13h is a recently identified subtype of Cas13 ribonuclease, with strong RNA cleavage activity and robust in vivo RNA knockdown efficiency. However, little is known regarding its biochemical properties and working mechanisms. Biochemical characterization of Cas13h1 indicated that it lacks in vitro pre-crRNA processing activity and adopts a central seed. The cleavage activity of Cas13h1 is enhanced by a R(G/A) 5'-PFS, and inhibited by tag:anti-tag RNA pairing. We determined the structures of Cas13h1-crRNA binary complex at 3.1 Å and Cas13h1-crRNA-target RNA ternary complex at 3.0 Å. The ternary complex adopts an elongated architecture, and encodes a nucleotide-binding pocket within Helical-2 domain to recognize the guanosine at the 5'-end of the target RNA. Base pairing between crRNA guide and target RNA disrupts Cas13h1-guide interactions, leading to dramatic movement of HEPN domains. Upon target RNA engagement, Cas13h1 adopts a complicated activation mechanism, including separation of HEPN catalytic residues and destabilization of the active site loop and NTD domain, to get activated. Collectively, these insights expand our understanding into Cas13 effectors.
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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.