Park Eddie, Guo Jiguang, Shen Shihao, Demirdjian Levon, Wu Ying Nian, Lin Lan, Xing Yi
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Department of Microbiology & Parasitology, Medical School of Hebei University, Baoding, Hebei Province, 071002, China.
Genome Biol. 2017 Jul 28;18(1):143. doi: 10.1186/s13059-017-1270-7.
A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing.
In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure.
Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.
A到I的RNA编辑是RNA加工过程中的一个重要步骤，在该过程中，一些RNA分子中的特定腺苷在转录后被修饰为肌苷。RNA编辑已成为产生转录组多样性的一种广泛机制。然而，关于RNA编辑的变异和功能仍存在重大的知识空白。
为了确定基因变异对A到I RNA编辑的影响，我们通过将RNA编辑数量性状位点（edQTL）分析与等位基因特异性RNA编辑（ASED）分析相结合，整合了来自445个人类淋巴母细胞系的基因组和转录组数据。我们鉴定出1054个与顺式基因多态性相关的RNA编辑事件。此外，我们发现这些多态性中的一部分与复杂性状或疾病的全基因组关联研究信号相关。最后，与随机顺式多态性相比，与RNA编辑变异相关的多态性在空间上更靠近其各自的编辑位点，并且对RNA二级结构有更显著的影响。
我们的研究揭示了遗传上不同个体之间RNA编辑中广泛存在的顺式变异，并阐明了这种变异对复杂性状和疾病可能产生的表型后果。
