Emerging Roles for 3′ UTRs in Neurons

The 3 ' untranslated regions (3 ' UTRs) of mRNAs serve as hubs for post-transcriptional control as the targets of microRNAs (miRNAs) and RNA-binding proteins (RBPs). Sequences in 3 ' UTRs confer alterations in mRNA stability, direct mRNA localization to subcellular regions, and impart translational control. Thousands of mRNAs are localized to subcellular compartments in neurons-including axons, dendrites, and synapses-where they are thought to undergo local translation. Despite an established role for 3 ' UTR sequences in imparting mRNA localization in neurons, the specific RNA sequences and structural features at play remain poorly understood. The nervous system selectively expresses longer 3 ' UTR isoforms via alternative polyadenylation (APA). The regulation of APA in neurons and the neuronal functions of longer 3 ' UTR mRNA isoforms are starting to be uncovered. Surprising roles for 3 ' UTRs are emerging beyond the regulation of protein synthesis and include roles as RBP delivery scaffolds and regulators of alternative splicing. Evidence is also emerging that 3 ' UTRs can be cleaved, leading to stable, isolated 3 ' UTR fragments which are of unknown function. Mutations in 3 ' UTRs are implicated in several neurological disorders-more studies are needed to uncover how these mutations impact gene regulation and what is their relationship to disease severity.