Riboswitches are cis-acting regulatory mRNA elements in bacteria, that modulate the expression of their associated genes in response to a cognate metabolite, operating either on the level of translation or transcription. Transcriptional riboswitches have to fold into functional structures as they are being synthesized and, only if transcription rates and ligand binding kinetics match, structured transcription intermediates are enabled to undergo ligand-dependent conformational refolding as a prerequisite for ligand-mediated gene expression. Therefore, transcription rates are of essential importance for functional riboswitch-mediated gene regulation. Here, we propose a generalized modeling framework for the kinetic mechanisms of transcriptional riboswitches. The formalism accommodates time-dependent transcription rates and changes of metabolite concentration and permits incorporation of variations in transcription rate depending on transcript length. We derive explicit analytical expressions for the fraction of transcripts that determine repression or activation of gene expression as a function of pause site location and its slowing down of transcription for the case of the (2’dG)-sensing riboswitch from Mesoplasma florum. Our modeling challenges the current view on the exclusive importance of metabolite binding to transcripts containing only the aptamer domain. Numerical simulations of transcription proceeding in a continuous manner under time-dependent changes of metabolite concentration further suggest that rapid modulations in concentration result in a reduced dynamic range for riboswitch function regardless of transcription rate, while a combination of slow modulations and small transcription rates ensures a wide range of finely tuneable regulatory outcomes.

核糖开关是细菌中的顺式作用调节性mRNA元件，其响应同源代谢物而调节其相关基因的表达，其在翻译或转录水平上起作用。转录核糖开关必须在合成时折叠成功能结构，并且只有在转录速率和配体结合动力学匹配时，结构化转录中间体才能进行配体依赖性构象重折叠，这是配体介导的基因表达的前提。因此，转录速率对于功能性核糖开关介导的基因调控至关重要。在这里，我们为转录核糖开关的动力学机制提出了一个通用的建模框架。形式主义适应随时间变化的转录速率和代谢物浓度的变化，并允许根据转录本长度引入转录速率的变化。对于（2'dG）感应核糖开关的情况，我们得出了转录物分数的明确分析表达式，该分数决定了基因表达的抑制或激活作为暂停位点位置的函数以及其减慢转录的速度。中型rum。我们的建模挑战了当前观点，即代谢物与仅包含适体结构域的转录本结合的排他性重要性。在代谢物浓度随时间变化的情况下，以连续方式进行转录的数值模拟进一步表明，浓度的快速调节导致核糖开关功能的动态范围减小，而与转录速率无关，而慢速调节和小的转录速率的结合则确保了各种可微调的监管成果。