Nuclear eukaryotic initiation factor 4E (eIF4E) colocalizes with splicing factors in speckles

The eukaryotic initiation factor 4E (eIF4E) plays a pivotal role in the con trol of protein synthesis. eIF4E binds to the mRNA 5' cap structure, m(7)Gp ppN (where N is any nucleotide) and promotes ribosome binding to the mRNA. It was previously shown that a fraction of eIF4E localizes to the nucleus ( Lejbkowicz, F., C. Goyer, A. Darveau, S. Neron, R. Lemieux, and N. Sonenber g. 1992. Proc. Natl. Acad. Sci. USA. 89: 9612-9616). Here, we show that the nuclear eIF4E is present throughout the nucleoplasm, but is concentrated i n speckled regions. Double label immunofluorescence confocal microscopy sho ws that eIF4E colocalizes with Sm and U1snRNP. We also demonstrate that pIF 4E is specifically released from the speckles by the cap analogue m(7)GpppG in a cell permeabilization assay. However, eIF4E is not released from the speckles by RNase A treatment, suggesting that retention of eIF4E in the sp eckles is not RNA-mediated. 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazol e (DRB) treatment of cells causes the condensation of eIF4E nuclear speckle s. In addition, overexpression of the dual specificity kinase, Clk/Sty, but not of the catalytically inactive form, results in the dispersion of eIF4E nuclear speckles.