Experimental methods to study protein–nucleic acid interactions

The interactions between proteins and nucleic acids regulate gene expression at transcriptional, post-transcriptional, and translational levels and often dictate the fate of cellular metabolism in physiological conditions and disease. To appreciate more in-depth the regulatory implications of these interactions and the pathological consequences of their disruption, it is necessary to identify the highest possible number of protein domains and DNA/RNA sequences and structures involved and to reveal the signaling cascades they activate. The tools in our hands are becoming increasingly sophisticated and precise in helping determine the main actors involved and how they modulate each other. Starting from in vitro single-molecule interaction techniques to their validation and implementations in cells, this chapter wants to offer an overview of the state-of-the-art experimental methods available to the scientific community to identify and investigate proteins and nucleic-acid-binding partners.