Cotranscriptional kinetic folding of RNA secondary structures including pseudoknots

TL;DR

This paper introduces a kinetic model for RNA secondary structure formation, including pseudoknots, that accounts for cotranscriptional effects, providing more accurate predictions of RNA folding pathways during synthesis.

Contribution

It presents a novel single-nucleotide resolution kinetic model and stochastic simulation method that incorporate transcriptional elongation, advancing understanding of RNA folding dynamics.

Findings

Model predicts biologically relevant conformations

Simulation captures cotranscriptional folding pathways

Provides quantitative insights into RNA folding kinetics

Abstract

Computational prediction of RNA structures is an important problem in computational structural biology. Studies of RNA structure formation often assume that the process starts from a fully synthesized sequence. Experimental evidence, however, has shown that RNA folds concurrently with its elongation. We investigate RNA secondary structure formation, including pseudoknots, that takes into account the cotranscriptional effects. We propose a single-nucleotide resolution kinetic model of the folding process of RNA molecules, where the polymerase-driven elongation of an RNA strand by a new nucleotide is included as a primitive operation, together with a stochastic simulation method that implements this folding concurrently with the transcriptional synthesis. Numerical case studies show that our cotranscriptional RNA folding model can predict the formation of conformations that are favored in actual biological systems. Our new computational tool can thus provide quantitative predictions and offer useful insights into the kinetics of RNA folding.