The molecular basis for the regulation of the cap-binding complex by the importins

Abstract

The binding of capped RNAs to the cap-binding complex (CBC) in the nucleus, and their dissociation from the CBC in the cytosol, represent essential steps in RNA-processing. Here we show how the nucleocytoplasmic transport proteins, importin-α and importin-β, play key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.2 Å resolution x-ray structure for a CBC-importin-α complex that provides a detailed picture for how importin-α binds to the CBP80 subunit of the CBC. Through a combination of biochemical studies, x-ray crystallographic information, and small-angle scattering experiments, we then determined how importin-β binds to the CBC through its CBP20 subunit. Together, these studies enable us to propose a model describing how importin-β stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export.