Computationally Reconstructing RNA Folding Pathways with Co-Transcriptional SHAPE-Seq

Co-transcriptional folding of RNAs happens every time an RNA is synthesized in the cell, making it an important process that underlies many conserved RNA functions. Formation of RNA structure happens during RNA transcription, and the final folded structure can depend greatly on the folding pathway. However, our understanding of RNA co-transcriptional folding is hampered by a lack of computational methods that can accurately determine these intricate folding pathways. Existing RNA folding algorithms often do not consider co-transcriptional folding. Even those that do consider co-transcriptional effects still require improvements in accuracy and have limitations such as being unable to take experimental data as input. Here we present a computational method that uses co-transcriptional SHAPE-Seq data, which can uncover nucleotide-resolution structural information for each intermediate length of an RNA during synthesis, to reconstruct the folding pathway of RNAs.