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. Author manuscript; available in PMC: 2013 Jul 15.
Published in final edited form as: Cold Spring Harb Symp Quant Biol. 2011 Mar 29;75:127–134. doi: 10.1101/sqb.2010.75.028

Figure 2.

Figure 2

Binding of karyopherin IMPβ to CBP80-bound IMPα, rather than the pioneer round of translation, promotes replacement of CBP80-CBP20 (CBC) by eIF4E at mRNA caps, as in Figure 1. However, here, IMPα is shown to be a constituent of CBC by virtue of its direct contact with CBP80. IMPα binds the bipartite nuclear localization signal of CBP80 on unspliced pre-RNA, possibly concomitantly with CBC binding to nascent transcripts. The pioneer round of translation has no detectable effects on either the association of IMPα with CBC or replacement of CBC by eIF4E. Instead, the interaction of the karyopherin IMPβ with IMPα in the cytoplasm promotes replacement of CBC by eIF4E. Replacement involves RAN-GTP-mediated delivery of nuclear IMPβ to the cytoplasm. GTPase-activating protein RAN-GAP together with RAN-binding protein (RANBP)1 converts RAN-GTP-IMPβ to RAN-GDP and IMPβ to promote IMPβ binding to IMPα-CBC (Dias et al. 2009; Sato and Maquat 2009). Replacement of CBC by eIF4E is followed by the movement of IMPβ-IMPα-CBC to nuclei. Once in the nucleus, IMPβ dissociates from IMPα-CBC. This frees IMPα-CBC to bind to the 5′ cap of newly made transcripts to function again in nuclear export and the cytoplasmic remodeling of mRNP.