Substrate Recognition and Specificity of Double-Stranded RNA Binding Proteins

Abstract

Recognition of double stranded (ds) RNA fragments is an important part of many cellular pathways, including RNA silencing, viral recognition, RNA editing, processing and transport. dsRNA recognition is often achieved by dsRNA binding domains (dsRBDs). We use atomistic molecular dynamics simulations to explain the binding of transactivation response RNA binding protein (TRBP) dsRBDs to dsRNA substrates, and their lack of binding to dsDNA and DNA-RNA hybrids. Our simulations confirm that dsRBDs bind more favorably to dsRNA than to DNA-RNA and dsDNA duplexes, in agreement with experimental observations. The dsRNA is recognized by dsRBDs through the A-form of both major and minor grooves and by the chemical properties of RNA bases, which have 2'-hydroxyl groups on their sugar rings. Our simulations show that the form of the DNA-RNA duplex can be modulated by dsRBD proteins, potentially explaining how some dsRBD proteins can bind weakly to DNA-RNA hybrids.