VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation.

Yoon, Peter H; Docter, Trevor A; Zhang, Zeyuan Terry; Loi, Kenneth; Lopez, Santiago C; Valentin-Alvarado, Luis E; Tuck, Owen T; Brohawn, Stephen G et al. · Science · 2026

basic_science · Level V

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Abstract

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo-electron microscopy structures that help explain the mechanism of target engagement. Vipr protomers oligomerize along the vrRNA to form a right-handed helical filament, sequestering each GGY motif and positioning the adjacent NN bases for target base pairing. DNA binding, in which every third nucleotide is skipped, results in a gapped vrRNA-DNA hybrid helix that encircles the nontarget DNA strand to form a geometric triplex. These findings suggest that triplex-mediated target-strand handoff could enable noncontiguous and programmable RNA-guided DNA recognition in VIPR systems.

Medical subject headings