Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, UCLA School of Dentistry, Los Angeles, CA, 90095, USA.
Division of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, CA, 90095, USA.
Sci Rep. 2017 Jun 13;7(1):3407. doi: 10.1038/s41598-017-03390-9.
Neuronal cells express considerable plasticity responding to environmental cues, in part, through subcellular mRNA regulation. Here we report on the extensive changes in distribution of mRNAs in the cell body and axon compartments of peripheral sensory neurons and the 3' untranslated region (3'UTR) landscapes after unilateral sciatic nerve entrapment (SNE) injury in rats. Neuronal cells dissociated from SNE-injured and contralateral L4 and L5 dorsal root ganglia were cultured in a compartmentalized system. Axonal and cell body RNA samples were separately subjected to high throughput RNA sequencing (RNA-Seq). The injured axons exhibited enrichment of mRNAs related to protein synthesis and nerve regeneration. Lengthening of 3'UTRs was more prevalent in the injured axons, including the newly discovered alternative cleavage and polyadenylation of NaV1.8 mRNA. Alternative polyadenylation was largely independent from the relative abundance of axonal mRNAs; but they were highly clustered in functional pathways related to RNA granule formation in the injured axons. These RNA-Seq data analyses indicate that peripheral nerve injury may result in highly selective mRNA enrichment in the affected axons with 3'UTR alterations potentially contributing to the mechanism of neuropathic pain.
神经元细胞在响应环境线索时表现出相当大的可塑性，部分原因是通过亚细胞 mRNA 调节。在这里，我们报告了在大鼠单侧坐骨神经嵌压 (SNE) 损伤后，周围感觉神经元细胞体和轴突区的 mRNA 分布以及 3'非翻译区 (3'UTR) 景观的广泛变化。从 SNE 损伤和对侧 L4 和 L5 背根神经节分离的神经元细胞在分隔的系统中培养。将轴突和细胞体 RNA 样本分别进行高通量 RNA 测序 (RNA-Seq)。受伤的轴突富集了与蛋白质合成和神经再生相关的 mRNAs。在受伤的轴突中，3'UTR 的延长更为普遍，包括新发现的 NaV1.8 mRNA 的选择性剪接和多聚腺苷酸化。选择性多聚腺苷酸化在很大程度上独立于轴突 mRNAs 的相对丰度;但它们高度聚集在与受伤轴突中 RNA 颗粒形成相关的功能途径中。这些 RNA-Seq 数据分析表明，周围神经损伤可能导致受影响轴突中高度选择性的 mRNA 富集，3'UTR 的改变可能有助于神经病理性疼痛的机制。
