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

中文翻译：

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5'UTR 序列在 BDNF mRNA 树突运输中的独特作用：BDNF 剪接变体空间代码的附加机制


神经营养蛋白脑源性神经营养因子 (BDNF) 由多个二分转录本编码。每个 BDNF 转录本由 11 个选择性剪​​接外显子中的一个组成，其中包含 5' 非翻译区 (UTR)，以及一个包含编码序列 (CDS) 和具有两种变体（短和长）的 3'UTR 的共同外显子。在神经元中，BDNF mRNA变异体具有明显的亚细胞分布，构成“空间密码”，外显子1、3、5、7和8位于神经元胞体，外显子4延伸到近端树突，外显子2和6到达远端树突。 。我们之前表明 CDS 编码组成型树突靶向信号 (DTS)，并且 3'UTR 短和 3'UTR 长都包含活性依赖性 DTS。然而，单个 5'UTR 外显子在 mRNA 分选中的作用仍不清楚。在这里，我们测试了每种不同 BDNF 5'UTR 影响绿色荧光蛋白 (GFP) 报告基因 mRNA 亚细胞定位的能力。我们发现外显子 2 剪接亚型（2a、2b 和 2c）诱导 GFP 报告基因 mRNA 向远端树突片段形成组成型树突靶向。其他亚型不影响 GFP-mRNA 树突运输。通过生物信息学分析，我们在外显子 2a、2b 和 2c 中确定了五个独特的顺式元件，它们可能有助于构建 DTS。这项研究提供了有关 BDNF mRNA 变体细胞分选调节机制的更多信息。