Molecular dissection of the eukaryotic initiation factor 4E (eIF4E) export-competent RNP.

The eukaryotic translation initiation factor 4E (eIF4E) controls gene expression through its effects on mRNA export and cap-dependent translation, both of which contribute to its oncogenic potential. In contrast to its translation function, the mRNA export function of eIF4E is poorly understood. Using an RNP isolation/mass spectrometry approach, we identified candidate cofactors of eIF4E mRNA export including LRPPRC. This protein associates with mRNAs containing the eIF4E-sensitivity element (4E-SE), and its overexpression alters the nuclear export of several eIF4E-sensitive mRNAs. LRPPRC-mediated alteration of eIF4E's mRNA export function requires the integrity of its eIF4E-binding site and it coincides with the subcellular re-distribution of eIF4E. The eIF4E export RNP is distinct in composition from the bulk mRNA export pathway, in that eIF4E- and eIF4E-sensitive mRNAs do not associate with general mRNA export factors such as TAP/NXF1 or REF/Aly. Our data indicate that mRNA export pathways have evolved for specific mRNAs enabling the differential regulation of biochemical pathways by modulating the expression of groups of genes at the level of their export.