A Formalization of Co-Transcriptional Splicing as an Operation on Formal Languages

📅 2025-04-17
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RNA co-transcriptional splicing is inherently unpredictable and difficult to program. Method: We introduce the first computational framework for co-transcriptional splicing based on bounded/unbounded hairpin deletion language operations, formalizing DNA template design as a language operation problem. Integrating formal language theory, computational complexity analysis, and RNA secondary structure constraints, we systematically characterize the hierarchy of language families corresponding to four splicing operations. Contribution/Results: We prove, for the first time, that both linearly and logarithmically bounded hairpin deletion are Turing-complete. Our work establishes the closure properties of co-transcriptional splicing languages and determines the computational complexity of template constructibility. It provides a rigorous theoretical foundation and methodological toolkit for controllable, predictable RNA sequence generation and programmable RNA nanostructure design.

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📝 Abstract
RNA co-transcriptionality is the process where RNA sequences are spliced while being transcribed from DNA templates. This process holds potential as a key tool for molecular programming. Co-transcriptional folding has been shown to be programmable for assembling nano-scale RNA structures, and recent advances have proven its Turing universality. While post-transcriptional splicing has been extensively studied, co-transcriptional splicing is gaining attention for its potential to save resources and space in molecular systems. However, its unpredictability has limited its practical applications. In this paper, we focus on engineering co-transcriptional splicing, moving beyond natural occurrences to program RNA sequences that produce specific target sequences through DNA templates. We introduce a formal model of co-transcriptional splicing, defined by constant-, linear-, and logarithmic-bounded hairpin deletion operations, as well as an unbounded hairpin deletion operation. We examine the complexity of the template constructability problem associated with these operations and study the closure properties of the languages they generate, providing insights for RNA template design in molecular programming systems.
Problem

Research questions and friction points this paper is trying to address.

Modeling co-transcriptional splicing for RNA sequence programming
Analyzing complexity of DNA template constructability problem
Studying language closure properties for RNA template design
Innovation

Methods, ideas, or system contributions that make the work stand out.

Formal model of co-transcriptional splicing operations
DNA templates program RNA target sequences
Analyze complexity and closure properties
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Da-Jung Cho
Da-Jung Cho
Yonsei University
Formal language and automata theoryBio-computing
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S. Fazekas
Graduate School of Engineering Science, Akita University, 1-1 Tegatagakuen-machi, Akita City, 010-0852, Akita, Japan.
S
Shinnosuke Seki
University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, 1828585, Tokyo, Japan.
M
Max Wiedenhoft
Department of Computer Science, Kiel University, Christian-Albrechts-Platz 4, Kiel, 24118, Schleswig-Holstein, Germany.