| Post-transcriptional gene regulation controls stability, localization, and/or translation of many eukaryotic mRNAs, usually by means of cis-elements present in the 3'-untranslated region (3'-UTR). In neurons, specific mRNAs are localized to the dendrites where they are translated constitutively or conditionally in an activity-dependent manner. This localization and local translation is essential for dendrite development and synaptic plasticity.;Regions within the 3'-UTRs of 7 dendritically localized mRNAs, called dendritic targeting elements or DTEs, have been shown to be necessary and sufficient for localization. Dendritic targeting elements and other dendritically localized sequences may contain a common dendritic localization motif. In other systems mRNA localization elements have taken the form of short contiguous motifs, short interspersed repeats, or extensive RNA secondary structure.;Here, motif-finding and RNA secondary-structure prediction tools were applied to dendritically localized sequences to identify a common dendritic localization element. A common contiguous motif or set of short interspersed repeats was not discovered, but mammalian DTEs were found to contain conserved RNA secondary structures which are more stable than expected by random chance. Three stemloops in the Map2 DTE and one in the Ddn DTE were found to be highly conserved among mammals and were cloned for experimental verification of involvement in localization.;Alternative polyadenylation of dendritically localized transcripts has the potential to change the 3'-UTR so that the dendritic localization element is excluded, producing a non-localizing transcript. The potential alternative polyadenylation of 23 dendritically localized genes was investigated here. Putative 3'-processing sites determined by EST-to-genome alignment, EST quality and tissue, flanking sequence content, evolutionary conservation, and additional attributes were used to decide if an alternative 3'-processing site is likely functional. Strong evidence of alternative polyadenylation, primarily through 3'-UTR truncation, was found for 15 of the mRNAs examined. The localization of the short and long isoforms of Bdnf and Creb1 was tested using in situ hybridization of mouse hippocampus sections. |
