Investigating RNA-ligand binding specificity by FT-ICR MS

Interactions between ribonucleic acids (RNA) and different binding partners (e.g., proteins or drugs) play a key role in many biological processes (e.g., protein biosynthesis and viral replication). Accordingly, human and viral RNA is a promising target for the development of therapeutics against a variety of diseases. The goal of this project is to better understand how exactly native ligands and potential drugs interact with ribonucleic acids to enable advances in RNA structural biology research and to promote the development of RNA-targeted drugs. To gain new insights into the recognition and binding of ligands to RNA, Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) will be used. Unlike conventional experiments in solution, this method can determine binding sites of RNA-ligand complexes with defined stoichiometry (for example, complexes consisting of one RNA and two drug molecules). Moreover, we will perform experiments to investigate the lifetimes of RNA-ligand complexes with different stoichiometries. By studying the intricate interplay of stoichiometry, binding sites, and lifetimes of RNA-ligand complexes, we hope to uncover previously unknown principles of how RNA and ligands assemble into biologically functional complexes and to better understand the specificity of RNA-ligand interactions.