3'UTR of mRNA Encoding CPEB Protein Orb2 Plays an Essential Role in Intracellular Transport in Neurons.

Intracellular trafficking plays a critical role in the functioning of highly polarized cells, such as neurons. Transport of mRNAs, proteins, and other molecules to synaptic terminals maintains contact between neurons and ensures the transmission of nerve impulses. Cytoplasmic polyadenylation element binding (CPEB) proteins play an essential role in long-term memory (LTM) formation by regulating local translation in synapses. Here, we show that the 3'UTR of the CPEB gene is required for targeting the mRNA and protein to synapses and that this localization is important for LTM formation. When the 3'UTR is deleted, the mRNAs and proteins fail to localize in synaptic fractions, and pronounced LTM deficits arise. We found that the phenotypic effects of the 3'UTR deletion were rescued by introducing the 3'UTR from the another CPEB gene. In contrast, the phenotypic effects of the 3'UTR deletion were not rescued by the 3'UTR from one of the α-tubulin genes. Our results show that the mRNAs must be targeted to the correct locations in neurons and that proper targeting depends upon sequences in the 3'UTR.