Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University, Atlanta, GA 30322, USA.
Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cells. 2022 Jun 17;11(12):1949. doi: 10.3390/cells11121949.
Neuropsychiatric diseases are among the most common brain developmental disorders, represented by schizophrenia (SZ). The complex multifactorial etiology of SZ remains poorly understood, which reflects genetic vulnerabilities and environmental risks that affect numerous genes and biological pathways. Besides the dysregulation of protein-coding genes, recent discoveries demonstrate that abnormalities associated with non-coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs), also contribute to the pathogenesis of SZ. lncRNAs are an actively evolving family of non-coding RNAs that harbor greater than 200 nucleotides but do not encode for proteins. In general, lncRNA genes are poorly conserved. The large number of lncRNAs specifically expressed in the human brain, together with the genetic alterations and dysregulation of lncRNA genes in the SZ brain, suggests a critical role in normal cognitive function and the pathogenesis of neuropsychiatric diseases. A particular lncRNA of interest is , also known as and . Growing evidence suggests the function of in governing neuronal development and its potential roles as a risk factor and biomarker for SZ, which will be reviewed in this article. Moreover, we discuss the potential mechanisms through which regulates molecular pathways, including its subcellular localization and interaction with RNA-binding proteins, and how interruption to pathways may contribute to the pathogenesis of SZ.
神经精神疾病是最常见的脑发育障碍之一,以精神分裂症(SZ)为代表。SZ 的复杂多因素病因仍未被充分理解,这反映了遗传易感性和环境风险,这些因素影响着众多基因和生物学途径。除了蛋白质编码基因的失调外,最近的发现表明,与非编码 RNA(包括 microRNAs 和长非编码 RNA(lncRNAs)相关的异常也与 SZ 的发病机制有关。lncRNAs 是一类活跃进化的非编码 RNA,其长度大于 200 个核苷酸,但不编码蛋白质。一般来说,lncRNA 基因的保守性较差。大量特定于人类大脑表达的 lncRNA,以及 SZ 大脑中 lncRNA 基因的遗传改变和失调,表明它们在正常认知功能和神经精神疾病发病机制中具有关键作用。一个特别引人关注的 lncRNA 是 ,也称为 和 。越来越多的证据表明 在调节神经元发育中的功能及其作为 SZ 的风险因素和生物标志物的潜在作用,本文将对此进行综述。此外,我们还讨论了 调节分子途径的潜在机制,包括其亚细胞定位和与 RNA 结合蛋白的相互作用,以及 途径的中断如何导致 SZ 的发病机制。