eIF4E (green) exports transcripts with a particular stem loop structure (red), but PML (blue) interferes with their interaction.

Cells experiencing a nutrient boon take advantage by ramping up translation. One of the translation-boosting factors keeps the good times rolling by moonlighting as an mRNA export factor. On page 415, Culjkovic et al. now show that eIF4E sends a slew of proliferation-inducing transcripts into the cytoplasm, possibly for priority translation.

The moonlighting is nothing new for this translation initiation factor—boosting eIF4E was known to increase the nuclear export of transcripts for cyclin D1 and ornithine decarboxylase. But the authors now find that eIF4E has many nuclear targets, most of which encode proteins that promote survival and cell division. High levels of eIF4E increased the export of these messages and, consequently, levels of their proteins.

In the cytoplasm, eIF4E binds to the m7G that caps all mRNAs. But in the nucleus, eIF4E, together with as-yet unknown factors, recognize a structural element—a complex pair of stem loops—within the 3′ UTRs of its specific export targets.

Transcripts containing this element formed nuclear foci with eIF4E and its associated proteins. The multifunctional PML growth inhibitor binds to nuclear eIF4E and prevents transcripts from getting hold. PML is induced by genomic damage and other stresses—conditions in which proliferation is unwanted and potentially dangerous.

The eIF4E-dependent pathway is separate from bulk export that relies on NXF1, as it instead depends on the CRM1 export receptor. This separation might open up a VIP pathway to the cytoplasm for eIF4E-associated transcripts, giving them a head start on translation in response to growth factors and other extracellular conditions that call for proliferation.

Many cancer cells contain high levels of eIF4E, which is a promising target for small molecule inhibitors. Reducing eIF4E activity should curtail the export and translation of an entire network of proliferation-inducing transcripts.