  Riboswitches, structured elements in the untranslated regions of messenger
RNAs, regulate gene expression by binding specific metabolites. We introduce a
kinetic network model that describes the functions of riboswitches at the
systems level. Using experimental data for flavin mono nucleotide riboswitch as
a guide we show that efficient function, implying a large dynamic range without
compromising the requirement to suppress transcription, is determined by a
balance between the transcription speed, the folding and unfolding rates of the
aptamer, and the binding rates of the metabolite. We also investigated the
effect of negative feedback accounting for binding to metabolites, which are
themselves the products of genes that are being regulated. For a range of
transcription rates negative feedback suppresses gene expression by nearly 10
fold. Negative feedback speeds the gene expression response time, and
suppresses the change of steady state protein concentration by half relative to
that without feedback, when there is a modest spike in DNA concentration. A
dynamic phase diagram expressed in terms of transcription speed, folding rates,
and metabolite binding rates predicts different scenarios in
riboswitch-mediated transcription regulation.
