RNA Editome in Rhesus Macaque Shaped by Purifying Selection

作者：Jiayu Chen, Zhiyu Peng, Rongli Zhang, Xinzhuang Yang, Bertrand Chin‐Ming Tan, Huaying Fang, Chu‐Jun Liu, Mingming Shi, Zhiqiang Ye, Yong E. Zhang, Minghua Deng, Xiuqin Zhang, Chuan‐Yun Li · 发表于：PLoS Genetics · 年份：2014 · DOI：10.1371/journal.pgen.1004274 · 被引用次数：83 · 研究领域：RNA regulation and disease、CRISPR and Genetic Engineering、RNA and protein synthesis mechanisms

Understanding of the RNA editing process has been broadened considerably by the next generation sequencing technology; however, several issues regarding this regulatory step remain unresolved--the strategies to accurately delineate the editome, the mechanism by which its profile is maintained, and its evolutionary and functional relevance. Here we report an accurate and quantitative profile of the RNA editome for rhesus macaque, a close relative of human. By combining genome and transcriptome sequencing of multiple tissues from the same animal, we identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We verified 96.6% of editing sites in coding regions and 97.5% of randomly selected sites in non-coding regions, as well as the corresponding levels of editing by multiple independent means, demonstrating the feasibility of our experimental paradigm. Several lines of evidence supported the notion that the adenosine deamination is associated with the macaque editome--A-to-G editing sites were flanked by sequences with the attributes of ADAR substrates, and both the sequence context and the expression profile of ADARs are relevant factors in determining the quantitative variance of RNA editing across different sites and tissue types. In support of the functional relevance of some of these editing sites, substitution valley of decreased divergence was detected around the editing site, suggesting the evolutionary constraint in maintaining some of these editing subst...