Department of Neurological Surgery, University of Wisconsin, Madison, WI, United States.
Department of Neurological Surgery, University of Wisconsin, Madison, WI, United States; William S. Middleton Veterans Hospital, Madison, WI, United States.
Prog Neurobiol. 2020 Mar;186:101746. doi: 10.1016/j.pneurobio.2020.101746. Epub 2020 Jan 10.
In mammals, many classes of noncoding RNAs (ncRNAs) are expressed at a much higher level in the brain than in other organs. Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. The circRNAs are also highly enriched in the brain and increase continuously from the embryonic to the adult stage. Although the functional significance and mechanism of action of circRNAs are still being actively explored, they are thought to regulate the transcription of their host genes and sequestration of miRNAs and RNA binding proteins. Some circRNAs are also shown to have translation potential to form peptides. The expression and abundance of circRNAs seem to be spatiotemporally maintained in a normal brain. Altered expression of circRNAs is also thought to mediate several disorders, including brain-tumor growth, and acute and chronic neurodegenerative disorders by affecting mechanisms such as angiogenesis, neuronal plasticity, autophagy, apoptosis, and inflammation. This review discusses the involvement of various circRNAs in brain development and CNS diseases. A better understanding of the circRNA function will help to develop novel therapeutic strategies to treat CNS complications.
在哺乳动物中，许多类非编码 RNA（ncRNAs）在大脑中的表达水平远高于其他器官。最近的研究发现了一类新的 ncRNAs，称为环状 RNA（circRNA），它是由外显子、内含子或两者的exon-intron 反向剪接和融合形成共价闭环。circRNA 在大脑中也高度富集，并从胚胎期到成年期持续增加。虽然 circRNA 的功能意义和作用机制仍在积极探索中，但它们被认为可以调节其宿主基因的转录，并隔离 miRNA 和 RNA 结合蛋白。一些 circRNA 也具有翻译潜力，能够形成肽。circRNA 的表达和丰度似乎在正常大脑中具有时空维持性。circRNA 的表达改变也被认为通过影响血管生成、神经元可塑性、自噬、细胞凋亡和炎症等机制，介导包括脑肿瘤生长和急性及慢性神经退行性疾病在内的多种疾病。本文综述了各种 circRNA 在脑发育和中枢神经系统疾病中的作用。更好地了解 circRNA 的功能将有助于开发治疗中枢神经系统并发症的新的治疗策略。
