Rethinking RNA-binding proteins: Riboregulation challenges prevailing views

RNA-binding proteins (RBPs) are best known as effectors along the entire gene expression pathway and as constituents of RNA-protein machines such as the ribosome and the spliceosome. Around 1,000 RBPs account for these functions in mammalian cells. The total number of RBPs has recently more than tripled to include many "well-known" proteins such as metabolic enzymes or membrane proteins, sparking debate about the biological relevance of their RNA binding. We examine the experimental basis underlying the dramatic expansion of the RBPome, consider arguments that challenge its relevance, and discuss recent data that describe new RBP and RNA functions. We suggest that the scope of interplay between RNA and proteins is underexplored and that riboregulation of proteins represents an emerging theme in cell biology and translational medicine.