An activity-dependent switch to cap-independent translation triggered by eIF4E dephosphorylation

The rate of translation of egg-laying hormone (ELH) in Aplysia californica bag cell neurons rises after an afterdischarge (AD), the physiological trigger for egg-laying 1 . We found that the 5′ untranslated region (5′ UTR) of ELH possessed an internal ribosomal entry site (IRES), and that an AD was accompanied by a switch to cap-independent, IRES-mediated translation, indicating that the use of a cellular IRES can be regulated by physiological activity. Furthermore, the AD caused dephosphorylation of the initiation factor eIF4E, which was sufficient to increase use of the ELH IRES, showing that dephosphorylation of eIF4E can trigger a switch to IRES-mediated translation.