Efficient computation of co-transcriptional RNA-ligand interaction dynamics

• Published in: Methods (San Diego, Calif.) Calif.), 2018-07, Vol.143, p.70-76
• Main Authors: Wolfinger, Michael T., Flamm, Christoph, Hofacker, Ivo L.
• Format: Article
• Language: English
• Subjects: Binding Sites - genetics; Co-transcriptional folding; Computational Biology - methods; Energy landscape; Entomoplasmataceae - genetics; Kinetics; Ligands; Models, Biological; Nucleic Acid Conformation; Riboswitch; Riboswitch - genetics; RNA dynamics; RNA Folding; RNA, Bacterial - chemistry; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; RNA-ligand interaction; Transcription, Genetic
• ISSN: 1046-2023; 1095-9130
• DOI: 10.1016/j.ymeth.2018.04.036

•Co-transcriptional RNA-ligand interaction dynamics are simulated for riboswitches under kinetic control.•Ligand concentration and binding energy effects are modeled efficiently.•Our framework can be used in riboswitch design for synthetic biology applications. Riboswitches form an abundant class of cis-regulatory RNA elements that mediate gene expression by binding a small metabolite. For synthetic biology applications, they are becoming cheap and accessible systems for selectively triggering transcription or translation of downstream genes. Many riboswitches are kinetically controlled, hence knowledge of their co-transcriptional mechanisms is essential. We present here an efficient implementation for analyzing co-transcriptional RNA-ligand interaction dynamics. This approach allows for the first time to model concentration-dependent metabolite binding/unbinding kinetics. We exemplify this novel approach by means of the recently studied I-A 2′-deoxyguanosine (2′dG)-sensing riboswitch from Mesoplasma florum.