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周围神经损伤过程中可变剪接的转录景观。

Transcriptional landscape of alternative splicing during peripheral nerve injury.

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing, China.

出版信息

J Cell Physiol. 2019 May;234(5):6876-6885. doi: 10.1002/jcp.27446. Epub 2018 Oct 26.

DOI:10.1002/jcp.27446
PMID:30362529
Abstract

Alternative splicing (AS) regulates a variety of biological activities in numerous tissues and organs, including the nervous system. However, the existence and specific roles of AS events during peripheral nerve repair and regeneration remain largely undetermined. In the current study, by mapping splice-crossing sequence reads, we identified AS events and relevant spliced genes in rat sciatic nerve stumps following sciatic nerve crush. AS-related genes at 1, 4, 7, and 14 days post nerve crush were compared with those at 0 day to discover alternatively spliced genes induced by sciatic nerve crush. These injury-induced alternatively spliced genes were then categorized to diseases and biological functions, genetic networks, and canonical signaling pathways. Bioinformatic analysis indicated that these alternatively spliced genes were mainly correlated to immune response, cellular growth, and cellular function maintenance. Our study elucidated AS events following peripheral nerve injury and might help deepen our understanding of the molecular mechanisms underlying peripheral nerve regeneration.

摘要

选择性剪接 (AS) 调节着包括神经系统在内的众多组织和器官的多种生物学活动。然而,AS 事件在外周神经修复和再生过程中的存在和具体作用在很大程度上仍未确定。在本研究中,通过映射拼接交叉序列读段,我们在大鼠坐骨神经挤压后识别了坐骨神经残端中的 AS 事件和相关剪接基因。将神经挤压后 1、4、7 和 14 天的 AS 相关基因与 0 天的基因进行比较,以发现由坐骨神经挤压诱导的选择性剪接基因。这些由损伤诱导的选择性剪接基因随后被分类为疾病和生物学功能、遗传网络和经典信号通路。生物信息学分析表明,这些选择性剪接基因主要与免疫反应、细胞生长和细胞功能维持有关。我们的研究阐明了外周神经损伤后的 AS 事件,可能有助于深入了解外周神经再生的分子机制。

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