ArticleNucleic acids research2024
Unveiling the RNA-mediated allosteric activation discloses functional hotspots in CRISPR-Cas13a.
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 20 papers.
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Who cites it
20 citing papers in PubMed.
- A structural accessibility principle for LbuCas13a activation by noncontiguous DNA.Nucleic acids research · 2026Article
- Programmable kinetic barcoding for multiplexed RNA detection with Cas13a.Nature biomedical engineering · 2026Article
- Computation and deep-learning-driven advances in CRISPR genome editing.Nature structural & molecular biology · 2026Review
- Programmable pH-responsive DNA inter-strand matching (PRISM) for precision molecular band-pass actuation.Theranostics · 2026Article
- Functional Coupling and Evolutionary Relationships Between Toxin-Antitoxin Systems and CRISPR-Cas Systems.Toxins · 2025Review
- CRISPR anti-tag-mediated room-temperature RNA detection using CRISPR/Cas13a.Nature communications · 2025Article
- Sparse networks of conformational fluctuations communicate signals within proteins.bioRxiv : the preprint server for biology · 2025Article
- And… cut! - how conformational regulation of CRISPR-Cas effectors directs nuclease activity.The Biochemical journal · 2025Review
- Design Rules for Expanding PAM Compatibility in CRISPR-Cas9 from the VQR, VRER and EQR variants.bioRxiv : the preprint server for biology · 2025Article
- A Cryptic Binding Pocket Regulates the Metal-Dependent Activity of Cas9.bioRxiv : the preprint server for biology · 2025Article
- Graph Attention Neural Networks Reveal TnsC Filament Assembly in a CRISPR-Associated Transposon.bioRxiv : the preprint server for biology · 2025Article
- Article
- Unveiling Cas8 dynamics and regulation within a transposon-encoded Cascade-TniQ complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Flexibility in PAM Recognition Expands DNA Targeting in xCas9.bioRxiv : the preprint server for biology · 2025Article
- Dimerization of the deaminase domain and locking interactions with Cas9 boost base editing efficiency in ABE8e.Nucleic acids research · 2024Article
- Graph theory approaches for molecular dynamics simulations.Quarterly reviews of biophysics · 2024Article
- CRISPR-Cas target recognition for sensing viral and cancer biomarkers.Nucleic acids research · 2024Review
- Molecular mechanism for target RNA recognition and cleavage of Cas13h.Nucleic acids research · 2024Article
- New design strategies for ultra-specific CRISPR-Cas13a-based RNA detection with single-nucleotide mismatch sensitivity.Nucleic acids research · 2024Article
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Abstract
Cas13a is a recent addition to the CRISPR-Cas toolkit that exclusively targets RNA, which makes it a promising tool for RNA detection. It utilizes a CRISPR RNA (crRNA) to target RNA sequences and trigger a composite active site formed by two 'Higher Eukaryotes and Prokaryotes Nucleotide' (HEPN) domains, cleaving any solvent-exposed RNA. In this system, an intriguing form of allosteric communication controls the RNA cleavage activity, yet its molecular details are unknown. Here, multiple-microsecond molecular dynamics simulations are combined with graph theory to decipher this intricate activation mechanism. We show that the binding of a target RNA acts as an allosteric effector, by amplifying the communication signals over the dynamical noise through interactions of the crRNA at the buried HEPN1-2 interface. By introducing a novel Signal-to-Noise Ratio (SNR) of communication efficiency, we reveal critical allosteric residues-R377, N378, and R973-that rearrange their interactions upon target RNA binding. Alanine mutation of these residues is shown to select target RNA over an extended complementary sequence beyond guide-target duplex for RNA cleavage, establishing the functional significance of these hotspots. Collectively our findings offer a fundamental understanding of the Cas13a mechanism of action and pave new avenues for the development of highly selective RNA-based cleavage and detection tools.
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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.