Folding Kinetics of Riboswitch Transcriptional Terminators and Sequesterers

A golden buprestid found near Port Angeles
sparkles like an exotic jewel.

A paper that I started as a graduate student, Folding Kinetics of Riboswitch Transcriptional Terminators and Sequesterers, was recently published in Entropy.  I won't reproduce the paper here, but instead I wanted to give a layman's explanation of what we found.

A riboswitch is a piece of RNA that serves both as a detector of some kinds of molecules and a switch to turn a gene's expression on and off.  For example, bacteria might be able to consume a certain kind of nutrient.  If the nutrient was found in the bacteria's environment, it would turn on a gene to make some proteins that can metabolize the nutrient.  The bacteria could use a riboswitch to sense the nutrient and to turn on the gene to digest it.

Some riboswitches work at the time of gene transcription, and work by stopping the RNA polymerase from completing the messenger RNA.  This process is called transcriptional termination.  Obviously, these riboswitches must perform their task quickly, because the RNA polymerase is able to make a gene on the timescale of seconds.

Other riboswitches work at the time of gene translation, and work by preventing a ribosome from binding to the messenger RNA and making the related protein.  We call these sequesterers.  The messenger RNA can be present in the cytoplasm for minutes or hours, so these riboswitches have a much longer timescale on which they may perform their task.

All riboswitches, like proteins, must fold into a particular shape in order to perform their tasks.

Using the open-source ViennaRNA software package, we simulated the folding of thiamine pyrophosphate riboswitches that use either the mechanism of transcriptional termination or sequestration to control their related genes and study the time it takes each type of riboswitch to fold into its functional shape.  We find evidence that the transcriptional terminators, which must operate on a faster timescale than sequesterers, are naturally selected to fold more efficiently.