Comprehensive identification of internal structure and alternative splicing events in circular RNAs.
Comprehensive identification of internal structure and alternative splicing events in circular RNAs.
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全面鉴定环状RNA的内部结构和选择性剪接事件
DOI：
10.1038/ncomms12060
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发表时间：
2016-06-28
影响因子：
16.6
通讯作者：
Zhao F
中科院分区：
文献类型：
--
作者：
Gao Y;Wang J;Zheng Y;Zhang J;Chen S;Zhao F
虽然以前的研究表明，环状RNA（circRNA）并不完全包括mRNA外显子，没有研究广泛探讨其内部结构。通过将算法与长读段测序数据和实验验证相结合，我们首次全面研究了10个人类细胞系和62个果蝇样本中circRNA的内部组分，并揭示了circRNA中选择性剪接（AS）事件的普遍性。值得注意的是，很大比例的circRNA AS外显子几乎不能在mRNA中检测到，并且富含与mRNA外显子中富集的那些不同的剪接因子的结合位点。我们发现，AS事件circRNA有一个偏向于核定位，并表现出组织和发育阶段特异性的表达模式。这项研究表明，一个独立的调控的生物发生或衰减的AS事件的circRNA和鉴定的环状AS异构体提供了未来的研究circRNA的形成和功能的目标。
Although previous studies demonstrated circular RNAs (circRNAs) does not exclusively comprise mRNA exons, no study has extensively explored their internal structure. By combining an algorithm with long-read sequencing data and experimental validation, we, for the first time, comprehensively investigate internal components of circRNAs in 10 human cell lines and 62 fruit fly samples, and reveal the prevalence of alternative splicing (AS) events within circRNAs. Significantly, a large proportion of circRNA AS exons can hardly be detected in mRNAs and are enriched with binding sites of distinct splicing factors from those enriched in mRNA exons. We find that AS events in circRNAs have a preference towards nucleus localization and exhibit tissue- and developmental stage-specific expression patterns. This study suggests an independent regulation on the biogenesis or decay of AS events in circRNAs and the identified circular AS isoforms provide targets for future studies on circRNA formation and function.