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Riboswitches, a class of non-coding RNA elements located in the untranslated 5' stretch of certain
bacterial messenger RNAs (mRNA), have recently been recognized as important players in controlling
bacterial gene expression. The control is often exerted via the level of cellular metabolites that self-regulate
their production, binding directly to a riboswitch motif on the mRNA that encodes enzymes involved in their
biosynthesis. While gene expression regulation by riboswitches is wide-spread in bacteria, they are sparsely
found in human. Due to their abundance in bacteria and sophistication of small molecule sensing strategies,
in recent times, riboswitch represents promising drug target for antibiotics. Therefore, using different
physical chemistry concepts and tools I seek to understand and expand this amazing sensing ability of
riboswitches, in accord with their structural and functional responses under different environmental
conditions. Positively charged metal ion environment is essential to maintain the structural fold and thus
functions of RNA. Among different metal ions, magnesium is particularly important for the stability of RNA
because it can efficiently support a close assembly of negatively charged phosphate groups in an RNA fold.
Here, I will present my postdoctoral research which aims to develop a structure-based generalized
electrostatic model of RNA, integrated with the essential effects of RNA ion-atmosphere including counterion
condensation phenomenon. This model has spurred new possibilities encouraging us to deal with
substantially large length-scale and long-time scale processes those are associated with complex riboswitch
responses, both in the presence and absence of metabolite under different buffer conditions. In this spirit, I’ll
discuss how magnesium ion-atmosphere pre-organizes a non-coding RNA triplex that facilitates stable
metabolite-binding which, in turn, regulates the translation initiation process. I will also discuss how one can
control transcription ON-OFF switching in bacteria by tuning the ion-atmosphere of RNA. All the studies tie
together state-of-the-art enhanced sampling molecular simulations with our newly developed potential and
different biochemical experiments.
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