Dynamics in multi-domain protein recognition of RNA

Protein–RNA interactions play essential roles in gene regulation and RNA metabolism. While high-resolution structures have revealed principles of RNA recognition by individual RNA binding domains (RBDs), the presence of multiple RBDs in many eukaryotic proteins suggests additional modes of RNA recognition by combination and cooperation of these interactions. Recent structures, together with biochemical and biophysical studies have revealed novel principles of RNA recognition by multi-domain proteins. These examples highlight an important role for dynamics in RNA recognition, with mechanisms including fly-casting and conformational selection, and advocate the use of solution techniques for their analysis.

► Protein–RNA complexes are assembled by combining multiple weak interactions.
► Dynamics is not reflected in static structures of multi-domain protein–RNA complexes.
► Flexible linkers enable induced fit, fly-casting and conformational selection.
► Solution techniques such as NMR spectroscopy can reveal binding mechanisms.