Biological processes driven by protein-RNA interactions are crucial for cell health and viability. A detailed understanding of the relationships between structure, conformational states, and function of these biomolecules, as well as their role in membrane-less intracellular compartmentalization, is essential for building a more complete picture of the diverse roles of protein-RNA interactions in health and disease. Direct, real-time observations of individual proteins interacting with RNA are necessary to validate and refine current biological models. Single-molecule technologies provide an exciting opportunity to meet these challenges and study RNA-dependent protein function and activity in real time. Here, we present our efforts to enable further discoveries in protein-RNA interactions through the correlative combination of optical tweezers, fluorescence microscopy, and microfluidics. We highlight several examples where our technologies have advanced the understanding of RNA-based DNA editing tools, translational regulation, and RNA-protein condensates. Additionally, we demonstrate how our biochemistry tools facilitate the easy assembly of RNA substrates for single-molecule experiments. Finally, we show that advances in hybrid single-molecule methods have led to the development of an easy-to-use and stable instrument, which opens new avenues for research into protein-RNA interactions.
Rahmanseresht et al. (2026) studied this question.