The article "A Brave New World of RNA-Binding Proteins" by Hentze et al. (2018) reviews the recent advancements in understanding RNA-binding proteins (RBPs) and their roles in gene expression. The authors highlight the discovery of hundreds of new RBPs through proteome-wide studies, many of which lack classical RNA-binding domains (RBDs). These unorthodox RBPs have been found to play various biological roles, including regulating metabolism, cell cycle progression, and antiviral responses. The review discusses methods for identifying these RBPs, such as RNA interactome capture, and explores their potential functions, including the possibility that some RBPs may be regulated by RNA rather than controlling it. The authors also delve into the mechanisms of RNA binding by intrinsically disordered regions (IDRs) and the role of RNA in shaping protein-RNA interactions. They emphasize the need for further structural and functional studies to understand the roles of these novel RBPs and their interactions with RNA. The article concludes by discussing the potential implications of these findings for our understanding of gene regulation and disease.The article "A Brave New World of RNA-Binding Proteins" by Hentze et al. (2018) reviews the recent advancements in understanding RNA-binding proteins (RBPs) and their roles in gene expression. The authors highlight the discovery of hundreds of new RBPs through proteome-wide studies, many of which lack classical RNA-binding domains (RBDs). These unorthodox RBPs have been found to play various biological roles, including regulating metabolism, cell cycle progression, and antiviral responses. The review discusses methods for identifying these RBPs, such as RNA interactome capture, and explores their potential functions, including the possibility that some RBPs may be regulated by RNA rather than controlling it. The authors also delve into the mechanisms of RNA binding by intrinsically disordered regions (IDRs) and the role of RNA in shaping protein-RNA interactions. They emphasize the need for further structural and functional studies to understand the roles of these novel RBPs and their interactions with RNA. The article concludes by discussing the potential implications of these findings for our understanding of gene regulation and disease.