Biogenesis, identification, and function of exonic circular RNAs.
Biogenesis, identification, and function of exonic circular RNAs.
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DOI：
10.1002/wrna.1294
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发表时间：
2015-09
影响因子：
7.3
通讯作者：
Chuang, Trees-Juen
中科院分区：
文献类型：
--
作者：
Chen, Iju;Chen, Chia-Ying;Chuang, Trees-Juen
环状RNA（circRNA）在转录后过程中产生，其中单链RNA分子通过共价结合形成环状。以前，circRNA产物通常被认为是剪接中间体、副产物或异常剪接的产物。但最近，用于非共线性（NCL）RNA的全球研究的高通量RNA测序（RNA-seq）的快速进展，导致对这种类型的NCL RNA（即，circRNA），尤其是外显子circRNA（ecircRNA）。虽然ecircRNA的生物起源和功能大多是未知的，但一些ecircRNA是丰富的、高度表达的或进化保守的。一些ecircRNA已被证明影响microRNA调控，并可能在调节亲本基因转录，细胞增殖和RNA结合蛋白中发挥作用，表明它们作为诊断工具的功能潜力。迄今为止，通过分析RNA-seq数据，已经在来自不同物种的多种组织/细胞类型中鉴定出数千种ecircRNA。然而，ecircRNA候选物的检测涉及几个主要挑战，包括区分ecircRNA和其他类型的NCL RNA（例如，反式剪接RNA和遗传重排）;去除测序错误、比对错误和体外伪影;以及调和由使用不同生物信息学方法或在不同处理下生成的测序数据产生的异质性结果。这些挑战可能会严重阻碍对ecircRNA的理解。本文综述了ecircRNA的生物起源、鉴定、性质和功能，并讨论了一些尚未解决的问题。我们还评估了一些众所周知的circRNA检测方法的准确性（在灵敏度和精密度方面）。WIREs RNA 2015，6：563-579。doi：10.1002/wrna.1294如需与本文相关的更多资源，请访问WIREs网站。
Circular RNAs (circRNAs) arise during post‐transcriptional processes, in which a single‐stranded RNA molecule forms a circle through covalent binding. Previously, circRNA products were often regarded to be splicing intermediates, by‐products, or products of aberrant splicing. But recently, rapid advances in high‐throughput RNA sequencing (RNA‐seq) for global investigation of nonco‐linear (NCL) RNAs, which comprised sequence segments that are topologically inconsistent with the reference genome, leads to renewed interest in this type of NCL RNA (i.e., circRNA), especially exonic circRNAs (ecircRNAs). Although the biogenesis and function of ecircRNAs are mostly unknown, some ecircRNAs are abundant, highly expressed, or evolutionarily conserved. Some ecircRNAs have been shown to affect microRNA regulation, and probably play roles in regulating parental gene transcription, cell proliferation, and RNA‐binding proteins, indicating their functional potential for development as diagnostic tools. To date, thousands of ecircRNAs have been identified in multiple tissues/cell types from diverse species, through analyses of RNA‐seq data. However, the detection of ecircRNA candidates involves several major challenges, including discrimination between ecircRNAs and other types of NCL RNAs (e.g., trans‐spliced RNAs and genetic rearrangements); removal of sequencing errors, alignment errors, and in vitro artifacts; and the reconciliation of heterogeneous results arising from the use of different bioinformatics methods or sequencing data generated under different treatments. Such challenges may severely hamper the understanding of ecircRNAs. Herein, we review the biogenesis, identification, properties, and function of ecircRNAs, and discuss some unanswered questions regarding ecircRNAs. We also evaluate the accuracy (in terms of sensitivity and precision) of some well‐known circRNA‐detecting methods. WIREs RNA 2015, 6:563–579. doi: 10.1002/wrna.1294 For further resources related to this article, please visit the WIREs website.
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