Deep structural insights into RNA‐binding disordered protein regions

Recent efforts to identify RNA binding proteins in various organisms and cellular contexts have yielded a large collection of proteins that are capable of RNA binding in the absence of conventional RNA recognition domains. Many of the recently identified RNA interaction motifs fall into intrinsically disordered protein regions (IDRs). While the recognition mode and specificity of globular RNA binding elements have been thoroughly investigated and described, much less is known about the way IDRs can recognize their RNA partners. Our aim was to summarize the current state of structural knowledge on the RNA binding modes of disordered protein regions and to propose a classification system based on their sequential and structural properties. Through a detailed structural analysis of the complexes that contain disordered protein regions binding to RNA, we found two major binding modes that represent different recognition strategies and, most likely, functions. We compared these examples with DNA binding disordered proteins and found key differences stemming from the nucleic acids as well as similar binding strategies, implying a broader substrate acceptance by these proteins. Due to the very limited number of known structures, we integrated molecular dynamics simulations in our study, whose results support the proposed structural preferences of specific RNA‐binding IDRs. To broaden the scope of our review, we included a brief analysis of RNA‐binding small molecules and compared their structural characteristics and RNA recognition strategies to the RNA‐binding IDRs. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry. RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition. RNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions.