数字农科院2.0

Genome wide analysis of allele-specific circular RNAs in mammals and their role in cell proliferation

文献类型： 外文期刊

作者： Ying Ju Li;Hang Liu;Yue Dong Zhang;Aimin Li;Li Xia Pu;Yun Gao;Shu Run Zhang;Newton O. Otecko;Lu Liu;Yu Yan Liu;Min Sheng Peng;David M. Irwin;Chungen Yi;Wei Xie;Yan Qin;Zefeng Wang;Hong Jiang Wei;Zhong Yin Zhou;Ya Ping Zhang

作者机构：

关键词： Allele specific circRNA;Cell proliferation;CircRNA;Intronic mutation

期刊名称： Gene

ISSN： 0378-1119

年卷期： 2025 年 946 卷

页码：

收录情况： SCIE（2025版）

摘要： Circular RNAs (circRNAs) are a large class of widely expressed RNAs with covalently closed continuous structures. However, it is currently unknown if circRNAs shows allele-specific expression, as are the consequences of genetic variation on their circularization efficiency and subsequent biological function. Here, we propose a novel pipeline, ASE-circRNA, to accurately quantify both circRNA and their related linear RNA for each allele, and then assess the allele-specificity of the expression of a circular RNA. We identified and analyzed allele-specific circRNAs from human tissue, as well as brains from reciprocal crosses between pairs of highly divergent strains of both mice and pigs by next generation sequencing. Droplet digital PCR (ddPCR) was used to confirm the circularization efficiency measured by next generation sequencing. We found that variation in intron sequences affect the circularization efficiency of circRNAs. Furthermore, we demonstrate that a circRNA, circHK1, regulates the expression of POLR2A to influence the rate of cell proliferation. Our study provides new insight into the molecular mechanisms impacted by variation in genome sequence in the origin of human disease and phenotype.

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