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全面鉴定人类组织转录组中的可变剪接。

Comprehensive identification of alternative back-splicing in human tissue transcriptomes.

机构信息

Department of Thoracic Surgery, Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

出版信息

Nucleic Acids Res. 2020 Feb 28;48(4):1779-1789. doi: 10.1093/nar/gkaa005.

Abstract

Circular RNAs (circRNAs) are covalently closed RNAs derived from back-splicing of genes across eukaryotes. Through alternative back-splicing (ABS), a single gene produces multiple circRNAs sharing the same back-splice site. Although many ABS events have recently been discovered, to what extent ABS involves in circRNA biogenesis and how it is regulated in different human tissues still remain elusive. Here, we reported an in-depth analysis of ABS events in 90 human tissue transcriptomes. We observed that ABS occurred for about 84% circRNAs. Interestingly, alternative 5' back-splicing occurs more prevalently than alternative 3' back-splicing, and both of them are tissue-specific, especially enriched in brain tissues. In addition, the patterns of ABS events in different brain regions are similar to each other and are more complex than the patterns in non-brain tissues. Finally, the intron length and abundance of Alu elements positively correlated with ABS event complexity, and the predominant circRNAs had longer flanking introns and more Alu elements than other circRNAs in the same ABS event. Together, our results represent a resource for circRNA research-we expanded the repertoire of ABS events of circRNAs in human tissue transcriptomes and provided insights into the complexity of circRNA biogenesis, expression, and regulation.

摘要

环状 RNA(circRNAs)是一类共价封闭的 RNA,通过真核生物基因的反向剪接产生。通过选择性反向剪接(ABS),单个基因可以产生多个共享相同反向剪接位点的 circRNA。尽管最近发现了许多 ABS 事件,但 ABS 在 circRNA 生物发生中的程度以及它在不同人类组织中是如何调控的仍然难以捉摸。在这里,我们对 90 个人类组织转录组中的 ABS 事件进行了深入分析。我们观察到 ABS 大约发生在 84%的 circRNAs 中。有趣的是,选择性 5'反向剪接比选择性 3'反向剪接更为普遍,而且它们都是组织特异性的,尤其是在脑组织中富集。此外,不同脑区 ABS 事件的模式彼此相似,比非脑组织中的模式更为复杂。最后,内含子长度和 Alu 元件的丰度与 ABS 事件的复杂性呈正相关,并且在同一 ABS 事件中,主要的 circRNAs 具有比其他 circRNAs 更长的侧翼内含子和更多的 Alu 元件。总的来说,我们的结果代表了 circRNA 研究的一种资源——我们扩展了人类组织转录组中 ABS 事件的 circRNA 目录,并深入了解了 circRNA 生物发生、表达和调控的复杂性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40f1/7038940/6c9718b553b0/gkaa005fig1.jpg

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