Secondary structure design for cotranscriptional 3D RNA origami wireframes

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A4 Artikkeli konferenssijulkaisussa

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en

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18

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31st International Conference on DNA Computing and Molecular Programming, DNA 31 2025, pp. 1-18, Leibniz International Proceedings in Informatics ; Volume 347

Abstract

We address the task of secondary structure design for de novo 3D RNA origami wireframe structures in a way that takes into account the specifics of a cotranscriptional folding setting. We consider two issues: firstly, avoiding the topological obstacle of “polymerase trapping”, where some helical domain cannot be hybridised due to a closed kissing-loop pair blocking the winding of the strand relative to the polymerase–DNA-template complex; and secondly, minimising the number of distinct kissing-loop designs needed, by reusing KL pairs that have already been hybridised in the folding process. For the first task, we present an efficient strand-routing method that guarantees the absence of polymerase traps for any 3D wireframe model, and for the second task, we provide a graph-theoretic formulation of the minimisation problem, show that it is NP-complete in the general case, and outline a branch-and-bound type enumerative approach to solving it. Key concepts in both cases are depth-first search in graphs and the ensuing DFS spanning trees. Both algorithms have been implemented in the DNAforge design tool (https://dnaforge.org) and we present some examples of the results.

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Publisher Copyright: © Pekka Orponen, Shinnosuke Seki, and Antti Elonen.

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Orponen, P, Seki, S & Elonen, A 2025, Secondary structure design for cotranscriptional 3D RNA origami wireframes. in J Schaeffer & F Zhang (eds), 31st International Conference on DNA Computing and Molecular Programming, DNA 31 2025., 6, Leibniz International Proceedings in Informatics, vol. 347, Schloss Dagstuhl - Leibniz-Zentrum für Informatik, pp. 1-18, International Conference on DNA Computing and Molecular Programming, Lyon, France, 25/08/2025. https://doi.org/10.4230/LIPIcs.DNA.31.6