Distinct role of 5′UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code

Abstract The neurotrophin Brain-derived neurotrophic factor (BDNF) is encoded by multiple bipartite transcripts. Each BDNF transcript composed one out of 11 alternatively spliced exons containing the 5′untranslated region (UTR), and common exon encompassing coding sequence (CDS) 3′UTR with two variants (short long). In neurons, mRNA have a distinct subcellular distribution, constituting “spatial code”, 1, 3, 5, 7 8 located in neuronal somata, 4 extending into proximal dendrites, 2 6 reaching distal dendrites. We previously showed that CDS encodes constitutive dendritic targeting signals (DTS) both 3′UTR-short 3′UTR-long contain activity-dependent DTS. However, role individual 5′UTR sorting remains unclear. Here, we tested ability each different 5′UTRs to affect localization green fluorescent protein (GFP) reporter mRNA. found splicing isoforms (2a, 2b, 2c) induced GFP towards segments. other did not GFP-mRNA trafficking. Through bioinformatic analysis, identified five unique cis-elements 2a, 2c which might contribute building This study provides additional information on mechanism regulating cellular variants.