Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, 414 E. Clark St., Vermillion, SD, 57069, USA.
Mol Neurobiol. 2021 Jun;58(6):2851-2861. doi: 10.1007/s12035-021-02306-z. Epub 2021 Jan 30.
Alternative splicing of genes in the central nervous system is ubiquitous and utilizes many different mechanisms. Splicing generates unique transcript or protein isoforms of the primary gene that result in shortened, lengthened, or reorganized products that may have distinct functions from the parent gene. Learning and memory genes respond selectively to a variety of environmental stimuli and have evolved a number of complex mechanisms for transcriptional regulation to act rapidly and flexibly to environmental demands. Their patterns of expression, however, are incompletely understood. Many activity-inducible genes generate transcripts by alternative splicing that have an unknown physiological or behavioral function. One such gene codes for the protein brain-derived neurotrophic factor (BDNF). BDNF is a neurotrophin whose expression is essential for cellular growth, synaptogenesis, and synaptic plasticity. It is an important model gene because of its complex structure and the variety of transcriptional mechanisms it displays for expression in response to external stimuli. Some of these are unexpected, or non-canonical, transcriptional control mechanisms that require further exploration in an activity-dependent context. In this review, a comparative genomics approach is taken to highlight the different forms of BDNF gene transcription including potential autoregulatory mechanisms. Modes of BDNF control have general implications for understanding the origins of several neurological disorders that are associated with reduced BDNF function.
基因在中枢神经系统中的选择性剪接是普遍存在的，它利用了许多不同的机制。剪接产生了初级基因的独特转录本或蛋白质同工型，从而导致缩短、延长或重组的产物，这些产物可能具有与亲本基因不同的功能。学习和记忆基因对各种环境刺激有选择性的反应，并进化出许多复杂的转录调控机制，以快速灵活地适应环境需求。然而，它们的表达模式尚不完全清楚。许多活性诱导基因通过选择性剪接产生具有未知生理或行为功能的转录本。其中一个这样的基因编码脑源性神经营养因子（BDNF）蛋白。BDNF 是一种神经营养因子，其表达对于细胞生长、突触形成和突触可塑性至关重要。它是一个重要的模型基因，因为它的复杂结构和它展示的各种转录机制，以响应外部刺激表达。其中一些是意想不到的或非典型的转录控制机制，需要在活动依赖的背景下进一步探索。在这篇综述中，采用比较基因组学的方法来突出 BDNF 基因转录的不同形式，包括潜在的自调节机制。BDNF 的控制模式对于理解几种与 BDNF 功能降低相关的神经疾病的起源具有普遍意义。
