Discovery of a trefoil knot in the RydC RNA: Challenging previous notions of RNA topology

• Published in: Journal of molecular biology Vol. 436; no. 6; p. 168455
• Main Authors: Niemyska, Wanda, Mukherjee, Sunandan, Gren, Bartosz A., Niewieczerzal, Szymon, Bujnicki, Janusz M., Sulkowska, Joanna I.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 15.03.2024
• Subjects: Entanglement of biomolecules; Molecular dynamics; RNA 3D structure; RNA folding; Topology in soft matter; RNA folding; Molecular dynamics; Entanglement of biomolecules; RNA 3D structure; Topology in soft matter
• ISSN: 0022-2836; 1089-8638; 1089-8638
• DOI: 10.1016/j.jmb.2024.168455

[Display omitted] •Discovery of the first knotted topology in a natural RNA molecule.•RydC RNA can self-tie via a native twisted loop conformation.•The trefoil knot is a conserved feature across all RydC-related RNAs.•Models used to predict RNA structures should take into account the correct topology. Knots are very common in polymers, including DNA and protein molecules. Yet, no genuine knot has been identified in natural RNA molecules to date. Upon re-examining experimentally determined RNA 3D structures, we discovered a trefoil knot 31, the most basic non-trivial knot, in the RydC RNA. This knotted RNA is a member of a small family of short bacterial RNAs, whose secondary structure is characterized by an H-type pseudoknot. Molecular dynamics simulations suggest a folding pathway of the RydC RNA that starts with a native twisted loop. Based on sequence analyses and computational RNA 3D structure predictions, we postulate that this trefoil knot is a conserved feature of all RydC-related RNAs. The first discovery of a knot in a natural RNA molecule introduces a novel perspective on RNA 3D structure formation and on fundamental research on the relationship between function and spatial structure of biopolymers.