RNA-binding proteins (RBPs) interact with RNA to form Ribonucleoprotein Particles (RNPs). The interaction between RBPs and their RNA partners are traditionally thought to be mediated by highly conserved RNA-binding domains (RBDs). Recently, high-throughput studies led to the discovery of hundreds of novel proteins and domains, of which many do not follow the classical definition of RNA-binding. Despite technological innovations, experimental screenings are currently limited to the detection of specific types of RNPs, underscoring the importance of computational methods for predicting novel RBPs and RNA interacting residues and interfaces. Here, we discuss major challenges in computational prediction of RBPs and RBDs and outline new strategies to circumvent current limitations of experimental techniques.
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