From Harvard Medical School and Division of Depression and Anxiety, McLean Hospital, Belmont, MA.
Harv Rev Psychiatry. 2018 Nov/Dec;26(6):364-373. doi: 10.1097/HRP.0000000000000206.
Understanding the complexity and regular function of the human brain is an unresolved challenge that hampers the identification of disease-contributing components and mechanisms of psychiatric disorders. It is accepted that the majority of psychiatric disorders result from a complex interaction of environmental and heritable factors, and efforts to determine, for example, genetic variants contributing to the pathophysiology of these diseases are becoming increasingly successful. We also continue to discover new molecules with unknown functions that might play a role in brain physiology. One such class of polymeric molecules is noncoding RNAs; though discovered years ago, they have only recently started to receive careful attention. Furthermore, recent technological advances in the field of molecular genetics and high-throughput sequencing have facilitated the discovery of a broad spectrum of RNAs that show no obvious coding potential but may provide additional layers of complexity and regulation to the molecular mechanisms underlying psychiatric disorders. Their exquisite enrichment and expression profiles in the brain may point to important functions of these RNAs in health and disease. This review will therefore aim to provide insight into the expression of noncoding RNAs in the brain, their function, and potential role in psychiatric disorders.
理解人类大脑的复杂性和正常功能是一个尚未解决的挑战,这阻碍了对导致疾病的成分和精神障碍发病机制的识别。人们普遍认为,大多数精神疾病是由环境和遗传因素的复杂相互作用引起的,并且确定例如导致这些疾病病理生理学的遗传变异的努力正变得越来越成功。我们还在不断发现具有未知功能的新分子,这些新分子可能在大脑生理学中发挥作用。一类这样的聚合分子是非编码 RNA;尽管它们多年前就被发现了,但直到最近才开始受到关注。此外,分子遗传学和高通量测序领域的最新技术进步促进了对广泛的非编码 RNA 的发现,这些 RNA 没有明显的编码潜力,但可能为精神障碍相关分子机制提供更多的复杂性和调控层。它们在大脑中的精细富集和表达谱可能表明这些 RNA 在健康和疾病中的重要功能。因此,本综述旨在深入了解非编码 RNA 在大脑中的表达、功能以及它们在精神疾病中的潜在作用。