The molecular basis for the regulation of the cap-binding complex by the importins.
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-alpha and importin-beta have key roles in regulating these events. As a first step toward understanding the molecular basis for this regulation, we determined a 2.2-A resolution X-ray structure for a CBC-importin-alpha complex that provides a detailed picture for how importin-alpha 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-beta binds to the CBC through its CBP20 subunit. Together, these studies enable us to propose a model describing how importin-beta stimulates the dissociation of capped RNA from the CBC in the cytosol following its nuclear export.
Dias
Sandra M G
SM
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Wilson
Kristin F
KF
Rojas
Katherine S
KS
Ambrosio
Andre L B
AL
Cerione
Richard A
RA
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D039502:Nuclear Cap-Binding Protein Complex / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism; D028901:alpha Karyopherins / Q000737:chemistry* / Q000378:metabolism; D028961:beta Karyopherins / Q000737:chemistry* / Q000378:metabolism
D039502:Nuclear Cap-Binding Protein Complex; D021122:Protein Subunits; D012315:RNA Caps; D028901:alpha Karyopherins; D028961:beta Karyopherins