Metal ion mediated riboswitch folding and cognate ligand sensing

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PhD; 2022; Solid state and structural chemistry unit

Riboswitches are noncoding RNA molecules that can control gene expression upon cognate ligand binding. Riboswitches are primarily present in bacteria and are crucial for bacteria's survival, which makes riboswitches attractive targets for discovering new antimicrobials. Designing drugs that target a riboswitch function can be accelerated by understanding the effect of physicochemical factors (like ions, temperature, pressure, cosolvents, and pH) on the riboswitch folding and cognate ligand binding. The magnesium (Mg2+) ions possess the unique capability to exhibit site-specific binding along the RNA chain and modulate the population of functionally relevant RNA tertiary structures. In this thesis, I have discussed the effect of Mg2+ on the folding thermodynamics and kinetics of the riboswitches and how cations assist riboswitches in attaining specific tertiary structures. I have provided insight into how the anionic cognate ligands bind to the polyanionic RNA backbone. Further, I have discussed the properties that contribute to cations' binding at specific riboswitch sites. I then highlighted, how riboswitch responds to the cognate ligand binding and transmits the ligand binding information to the gene expression machinery.