ABSTRACT:

RNA-binding proteins (RBPs) are traditionally associated with canonical RNA metabolism, including splicing, transport, translation, and decay. However, large-scale studies over the last decade have revealed a far broader and more complex landscape of RNA–protein networks. Remarkably, many proteins previously well studied for unrelated cellular functions have emerged as unconventional RBPs despite lacking classical RNA-binding domains. These findings suggest that RNA may play a much more pervasive role in cellular organization than previously appreciated.

An emerging concept referred to as “riboregulation” proposes that RNA itself can regulate protein localization, interactions, and function, thereby contributing directly to the spatial and functional organization of the cell. Understanding these mechanisms requires dedicated approaches to consolidate and integrate heterogeneous datasets across biological systems and experimental contexts.

I will present how the development of RBP2GO, a comprehensive resource for RBPs (rbp2go.dkfz.de), has enabled the identification of previously overlooked RNA–protein networks and RNA-mediated regulatory mechanisms in key cellular structures and pathways, including the mitotic apparatus and the microtubule cytoskeleton. I will also discuss our current efforts to expand and refine this resource to facilitate new discoveries in physiology and disease.