RNA-binding proteins: a lesson in repression

Abstract

Regulation of protein expression in neurons by controlling not only when, but where, mRNAs are translated is likely to play an important role in neuronal function. In this review I focus on the mRNA-binding proteins that control mRNA translation in neurons and how they may participate in local, synaptodendritic protein synthesis.

Figure 1.

mRNA translation repression and activation mediated by CPEB1. This schematic represents the steps thought to occur during the regulation of mRNA translation of CPEB1-bound mRNA. Initially, the mRNA is held in a translationally dormant state by CPEB1 binding to the CPE sequence in the 3′UTR. Translational repression is accomplished by the interaction of maskin with eIF4E. As with most 4E-BPs, maskin binds eIF4E at the same site that eIF4G binds, thus preventing the formation of the initiation complex. Presumably, mRNA translated in the dendrite are transported in this repressed state. After synaptic activation, CPEB1 phosphorylation (see text) results in the recruitment of cleavage and polyadenylation specificity factor (CPSF) to the hexanucleotide (HEX) sequence and the polyadenylation of the message by Gld2. This polyadenylation helps to override the maskin inhibition and eIF4G can now bind to eIF4E and establish the initiation of translation.