Research articleRat NEURL1 3′UTR is alternatively spliced and targets mRNA to dendrites

- The 3′UTR of Neuralized-like1 (NEURL1) mRNA exists in two splice variants (1743 and 1477 nt in length).
- The NEURL1 mRNA with spliced 3'UTR is expressed at low levels, reaching up to 1.65% of the levels of total NEURL1 transcripts.
- The spliced NEURL1 3′UTR is a target of nonsense-mediated decay.
- NEURL1 transcripts with spliced and full-length 3′UTRs are enriched in the neurites of primary hippocampal neurons.
- Both spliced and full-length NEURL1 3′UTRs can direct reporter mRNAs to the dendrites in primary hippocampal neurons.

Neuralized, an E3 ubiquitin ligase, interacts with and positively modulates the Notch pathway by promoting ubiquitination and subsequent endocytosis of its ligands. NEURL1 mRNA is dendritically localised in the dentate gyrus of an adult rat brain, implying that it may be locally translated, but its transport mechanisms remain unstudied.Here, we report the presence of a previously unknown, shorter splice-variant of rat NEURL1 3′UTR (1477 bp in length), and identify it as a potential target of nonsense-mediated decay. We show that endogenous NEURL1 mRNAs with both longer and shorter 3′UTRs are enriched in the neurites of cultured rat primary hippocampal neurons. Both NEURL1 3′UTRs can mediate transport of reporter mRNAs into dendrites in primary hippocampal neurons. By analysing the dendritic trafficking capacity of reporter mRNAs linked to various regions of longer or shorter NEURL1 3′UTR, we localise the dendritic targeting element (DTE) of spliced version of NEURL1 3′UTR to its first half, corresponding to the nucleotides 1-148 and 416-914 of the full-length 3′UTR. In contrast, the dendritic targeting capacity of the full-length NEURL1 3′UTR is abolished by splitting its 3′UTR in two halves (nt 1-914 and nt 915-1744), suggesting that slightly different DTE might mediate dendritic transport of the two transcripts.