Understanding the RNA-recognition mechanism of dsRBDs using TAR-RNA Binding Protein (TRBP) as a model system

Abstract

TAR RNA binding protein (TRBP) has been known for its involvement in the RNA interference (RNAi) pathway. TRBP aids the Dicer-mediated pre-miRNA cleavage and recruitment of the RISC complex. While doing so, TRBP binds to various pre-miRNAs & siRNA having differences in sequence, structure, or both. We proposed that TRBP adapts to accommodate such diverse RNA structures dynamically. Thus, it becomes imperative to understand how intrinsic protein dynamics plays a role in RNA recognition and binding. Previously, we have established the role of intrinsic and RNA-induced conformational exchange in the dsRBD1 of TRBP in shape-dependent RNA recognition. To take these investigations further, in this current study, we have focussed on the intrinsic and RNA-induced conformational dynamics of the double-stranded RNA-binding domain 2 (dsRBD2) of TRBP and compared it with the dsRBD1. We are proposing a dynamics-driven model of the two domains of TRBP which aids in the versatility of dsRNA-recognition & binding.