Co-transcriptional RNA folding
In the cell an RNA molecule starts to fold while it is still being made. The polymerase adds a few tens of nucleotides per second, and the 5′ part of the chain has long found a structure before the 3′ part exists. Structures formed early can persist as metastable states, so the final structure depends on the transcription history and not only on the sequence.
These posts describe the formalism for folding on a landscape that changes with every added nucleotide (BarMap), its application to riboswitches whose function depends on such intermediates, the inclusion of ligand binding into the kinetics, and the design of switches that take the transcriptional path into account. See co-transcriptional folding and BarMap in the glossary.
Co-transcriptional riboswitch modeling with ViennaRNA
A landscape-based method for modeling how cotranscriptional folding and ligand binding interact in kinetically controlled riboswitches, illustrated with the 2'dG riboswitch from Mesoplasma florum.
In silico design of ligand-triggered RNA switches
A computational workflow for designing ligand-triggered RNA switches, with emphasis on sequence design, folding kinetics, and candidate prioritization.
Co-transcriptional folding and metastable states in riboswitch function
This paper uses NMR spectroscopy to resolve transcription intermediates of the 2'dG riboswitch at single-nucleotide resolution, showing how transcript length and metastable states govern ligand-controlled switching.
BarMap and RNA folding on dynamic energy landscapes
BarMap models RNA folding on changing energy landscapes by linking macrostates between landscape snapshots, enabling efficient analysis of co-transcriptional and externally perturbed folding scenarios.
Folding kinetics of large RNAs
Kinwalker predicts folding trajectories of large RNAs by combining locally optimal substructures and kinetic heuristics, making co-transcriptional folding analysis feasible for molecules up to about 1500 nucleotides.