| 論文作者 |
Li, YJ; Liu, H; Zhang, YD; Li, AM; Pu, LX; Gao, Y; Zhang, SR; Otecko, NO; Liu, L; Liu, YY; Peng, MS; Irwin, DM; Yi, CG; Xie, W; Qin, Y; Wang, ZF; Wei, HJ; Zhou, ZY; Zhang, YP |
| 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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