Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Wiley Interdiscip Rev RNA. 2018 Jul;9(4):e1478. doi: 10.1002/wrna.1478. Epub 2018 Apr 14.
The first circular RNA (circRNA) was identified more than 40 years ago, but it was only recently appreciated that circRNAs are common outputs of many eukaryotic protein-coding genes. Some circRNAs accumulate to higher levels than their associated linear mRNAs, especially in the nervous system, and have clear regulatory functions that result in organismal phenotypes. The pre-mRNA splicing machinery generates circRNAs via backsplicing reactions, which are often facilitated by intronic repeat sequences that base pair to one another and bring the intervening splice sites into close proximity. When spliceosomal components are limiting, circRNAs can become the preferred gene output, and backsplicing reactions are further controlled by exon skipping events and the combinatorial action of RNA binding proteins. This allows circRNAs to be expressed in a tissue- and stage-specific manner. Once generated, circRNAs are highly stable transcripts that often accumulate in the cytoplasm. The functions of most circRNAs remain unknown, but some can regulate the activities of microRNAs or be translated to produce proteins. Circular RNAs can further interface with the immune system as well as control gene expression events in the nucleus, including alternative splicing decisions. Circular RNAs thus represent a large class of RNA molecules that are tightly regulated, and it is becoming increasingly clear that they likely impact many biological processes. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Evolution and Genomics > Computational Analyses of RNA.
第一个环状 RNA（circRNA）是在 40 多年前被发现的，但直到最近人们才意识到 circRNA 是许多真核蛋白编码基因的常见产物。一些 circRNA 的积累水平高于其相关的线性 mRNA，尤其是在神经系统中，并且具有明确的调节功能，从而导致生物体表型。前体 mRNA 剪接机制通过反式剪接反应产生 circRNA，这种反应通常由彼此碱基配对并使间隔的剪接位点接近的内含子重复序列所促进。当剪接体成分有限时，circRNA 可以成为首选的基因产物，反式剪接反应进一步受到外显子跳跃事件和 RNA 结合蛋白的组合作用的控制。这使得 circRNA 可以以组织和阶段特异性的方式表达。一旦产生，circRNA 就是高度稳定的转录本，通常在细胞质中积累。大多数 circRNA 的功能仍然未知，但有些可以调节 microRNA 的活性或被翻译产生蛋白质。环状 RNA 还可以与免疫系统相互作用，并控制细胞核中的基因表达事件，包括选择性剪接决定。因此，circRNA 代表了一类受到严格调控的 RNA 分子，越来越明显的是，它们可能影响许多生物学过程。本文属于以下类别：RNA 加工>剪接机制 RNA 结构和动态>RNA 结构对生物系统的影响 RNA 进化和基因组学>RNA 和核糖核蛋白进化 RNA 进化和基因组学>RNA 的计算分析。
