Wiley Interdiscip Rev RNA. 2025 Jul-Aug;16(4):16(4): e70020
mRNA translation is a highly orchestrated process that requires spatiotemporal control to ensure each protein is synthesized at the correct abundance, time, and location during human development and physiology. Classically, trans-acting RNA-binding proteins (RBPs) recognize cis-elements within mRNAs to provide one layer of gene-specific translational control. The function and properties of RBPs are diverse, with some harboring enzymatic capabilities, and can be multifaceted if present in larger RBP complexes. In this review, we focus on the role of Topoisomerase 3β (TOP3B) as a non-canonical RBP that is believed to influence the translation of select mRNAs and its connection with multiple human neurological disorders. Unlike any other encoded topoisomerase in the human genome, TOP3B is an mRNA-binding protein, catalytically favors RNA over DNA, and primarily localizes to the cytoplasm. Here we highlight important aspects of TOP3B as an RBP and raise multiple key questions for the field as a roadmap to better define its function in translational control and neuropathology. This article is categorized under: Translation > Regulation RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
Keywords: RNA‐binding protein; mRNA; neurological disease; translational control