Regulatory functions and pathological relevance of the MECP2 3'UTR in the central nervous system.
Regulatory functions and pathological relevance of the MECP2 3'UTR in the central nervous system.
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DOI：
10.1186/s13619-015-0023-x
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Pang ZP
中科院分区：
文献类型：
--
作者：
McGowan H;Pang ZP
甲基化CpG结合蛋白2（Methyl-CpG-binding protein 2，MeCP 2）是由MECP 2基因编码的一种转录调节因子和染色质重塑蛋白，广泛表达于中枢神经系统（CNS）的发育和维持中，在中枢神经系统的发育和维持中起重要作用。MeCP 2在迁移后神经元中高度富集，是神经元成熟所必需的，包括树突状分支和突触的发育。MECP 2中的功能丧失突变导致Rett综合征（RTT），这是一种以正常发育阶段为特征的衰弱性神经发育障碍，随后是里程碑和认知障碍的进行性丧失。虽然自从发现MeCP 2作为RTT的遗传原因以来，已经发现了大量关于MeCP 2的结构，功能和调节，包括其参与许多RTT相关综合征，这些综合征被称为MeCP 2谱疾病，但关于这种多功能蛋白质的许多内容仍然是谜。一个已经变得明显的明确事实是将MeCP 2蛋白水平维持在窄范围内的重要性，其限度可能取决于细胞类型和发育时间点。因此，MeCP 2可进行复杂的多因子调节。在这里，我们总结了MECP 2 3'非翻译区（UTR）在调节MeCP 2蛋白水平中的作用，以及该区域的突变如何导致自闭症和其他非RTT神经精神疾病。
Methyl-CpG-binding protein 2 (MeCP2), encoded by the gene MECP2, is a transcriptional regulator and chromatin-remodeling protein, which is ubiquitously expressed and plays an essential role in the development and maintenance of the central nervous system (CNS). Highly enriched in post-migratory neurons, MeCP2 is needed for neuronal maturation, including dendritic arborization and the development of synapses. Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a debilitating neurodevelopmental disorder characterized by a phase of normal development, followed by the progressive loss of milestones and cognitive disability. While a great deal has been discovered about the structure, function, and regulation of MeCP2 in the time since its discovery as the genetic cause of RTT, including its involvement in a number of RTT-related syndromes that have come to be known as MeCP2-spectrum disorders, much about this multifunctional protein remains enigmatic. One unequivocal fact that has become apparent is the importance of maintaining MeCP2 protein levels within a narrow range, the limits of which may depend upon the cell type and developmental time point. As such, MeCP2 is amenable to complex, multifactorial regulation. Here, we summarize the role of the MECP2 3' untranslated region (UTR) in the regulation of MeCP2 protein levels and how mutations in this region contribute to autism and other non-RTT neuropsychiatric disorders.