Expanded Expression Landscape and Prioritization of Circular RNAs in Mammals

Expanded Expression Landscape and Prioritization of Circular RNAs in Mammals
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哺乳动物中环状 RNA 的扩展表达景观和优先顺序

DOI:
10.1016/j.celrep.2019.02.078
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发表时间:
2019-03-19
期刊:
影响因子:
8.8
通讯作者:
Zhao, Fangqing
Zhao, Fangqing
中科院分区:
生物学1区
文献类型:
--
作者:
Ji, Peifeng;Wu, Wanying;Zhao, Fangqing

文献摘要

被引文献

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环状RNA(circRNA)正在成为各种生物和疾病过程的重要调节因子。为了全面了解circRNA的多样性并优先考虑其重要性,我们对来自人类,猕猴和小鼠的多种组织的circRNA库进行了大规模研究。我们分别从这三个物种中发现了总共104,388,96,675和82,321个circRNA,平均72.6%被成功组装成每个物种的全长转录本。使用这些全长circRNA,我们鉴定了数千种进化上保守的circRNA,这些circRNA对于功能筛选和优先级排序很有价值。通过构建物种特异性和保守基因共表达网络,我们在全球范围内推断circRNA功能,并优先考虑有前途的功能候选者。为了说明良好的先验知识如何有助于筛选功能候选者,我们使用circRNA共表达网络来优先考虑可能参与肝脏肿瘤发生的circRNA,并通过实验验证了它们的功能。
Circular RNAs (circRNAs) are emerging as essential regulators of various biological and disease processes. To comprehensively understand the diversity of circRNAs and prioritize their importance, we present a large-scale study of circRNA repertoires from multiple tissues from human, macaque, and mouse. We discovered totals of 104,388, 96,675, and 82,321 circRNAs from the three species, respectively, with an average of 72.6% being successfully assembled into full-length transcripts for each species. Using these full-length circRNAs, we identified thousands of evolutionarily conserved circRNAs that were valuable for functional screening and prioritization. By constructing both species-specific and conserved gene co-expression networks, we inferred circRNA functions on a global scale and prioritized promising functional candidates. To illustrate how well-established prior knowledge facilitates to screen functional candidates, we used the circRNA co-expression networks to prioritize circRNAs that may be involved in liver tumorigenesis and experimentally validated their functions.