Amazing stuff!
"“Researchers at Vilnius University in Lithuania introduced a new, more versatile genetic toolkit called the type IV-A CRISPR system. Described in a study published Oct. 29 in the journal Nature Communications, the system deactivate genes in an impermanent manner, giving researchers more control over gene activity…
by unraveling DNA’s double helix, the type IV-A system can stably but reversibly suppress a gene’s activity without having to cut its DNA.”"
"Scientists ... have discovered a unique way for cells to silence specific genes without cutting DNA. This groundbreaking research ... reveals a new way to silence genes akin to pressing a "pause" button on specific genetic instructions within cells.
The research team ... uncovered how cells use a specific system to locate and silence unwanted DNA. This system, which could eventually enable safer gene modifications, shows promise for repairing faulty genes that cause diseases.
“Unlike the well-known CRISPR gene-editing system, often described as molecular 'scissors,' the newly studied type IV-A CRISPR system does not cut genes. Instead, it uses an RNA-guided ‘effector’ complex to recruit an enzyme called DinG, which moves along DNA and silences targeted genes more subtly,” ..."
From the abstract:
"CRISPR-Cas mediated DNA-interference typically relies on sequence-specific binding and nucleolytic degradation of foreign genetic material. Type IV-A CRISPR-Cas systems diverge from this general mechanism, using a nuclease-independent interference pathway to suppress gene expression for gene regulation and plasmid competition. To understand how the type IV-A system associated effector complex achieves this interference, we determine cryo-EM structures of two evolutionarily distinct type IV-A complexes (types IV-A1 and IV-A3) bound to cognate DNA-targets in the presence and absence of the type IV-A signature DinG effector helicase. The structures reveal how the effector complexes recognize the protospacer adjacent motif and target-strand DNA to form an R-loop structure. Additionally, we reveal differences between types IV-A1 and IV-A3 in DNA interactions and structural motifs that allow for in trans recruitment of DinG. Our study provides a detailed view of type IV-A mediated DNA-interference and presents a structural foundation for engineering type IV-A-based genome editing tools."
New CRISPR system pauses genes, rather than turning them off permanently "Researchers in Lithuania present the molecular structure of a new, more-versatile CRISPR system for gene editing."
Vilnius University Researchers Uncover New Gene Silencing Mechanism (original news release)
Fig. 1: Structures of types IV-A1 and IV-A3.
Fig. 9: Model of type IV-A–mediated interference.
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