Rational Design of Riboswitches: papers to read

Wachsmuth, et al - De novo design of a synthetic riboswitch that regulates transcription termination

• engineered switch terminates transcription in the absence of theophylline (6.5 fold induction in presence of theophylline)
• model folding of many candidate switches in steps of 5-10 nt (to simulate different elongation speeds) using RNAfold
• find distribution of MFE in shuffled sequences to characterize those structures more/less stable than expected by chance

Beisel and Smolke - Design Principles for Riboswitch Function

• In this paper they develop a kinetics model for riboswitches that function in any of three ways: translational repression, transcriptional termination, and mRNA destabilization. The mathematical modelling involved differential equations to describe each step in the mechanism of transcription, ligand binding, translation, and RNA degradation. They emphasized the importance of the relative rates of reversible steps such as RNA folding and ligand binding to irreversible steps such as transcription termination and RNA degradation. They built theophylline riboswitches to confirm important aspects of their model.

Dixon, et al - Reengineering Orthogonally Selective Riboswitches

Rieder, et al (referenced by Dixon)- Ligand-Induced Folding of the Adenosine Deaminase A-Riboswitch and Implications on Riboswitch Translational Control

Perdizet, et al - Transcriptional pausing coordinates folding of the aptamer domain and the expression platform of a riboswitch

Ceres, et al (Mar 2013) - Modularity of Select Riboswitch Expression Platforms Enables Facile Engineering of Novel Genetic Regulatory Devices

• OFF switches

Ceres, Trausch and Batey (Dec 2013) - Engineering modular ‘ON’ RNA switches using biological components