Structural differences between the closely related RNA helicases, UAP56 and URH49 fashions distinct functional apo-complexes

Abstract Messenger RNA export is a regulated pathway that control gene expression and specific physiological events. In humans, closely related RNA helicases, UAP56 and URH49 shape selective mRNA export pathways through distinct apo-complex formation and remodeling to similar ATP-complex to achieve precise gene regulation. The difference in apo-complex is the key to functional divergence. However, the profile of the apo-complex formed by URH49 (named apo-AREX complex) and why UAP56 and URH49 exhibit distinct complex formation remain unknown. Here, we investigated unidentified apo-AREX components. RUVBL1, RUVBL2, ILF2, ILF3, and HNRNPM were physically and functionally associated with URH49, indicating the key components of the apo-AREX complex. Integrating analysis of crystal structure and complex formation of UAP56/URH49 chimera mutants demonstrated that their structural features contribute to respective complex formation. This study provides insights into the specific function of two helicases and into how two helicases diverged from a single ancestral gene, Sub2.