Genome wide analyses uncover allele-specific RNA editing in human and mouse
Zhong-Yin Zhou, Yue Hu, Aimin Li, Ying-Ju Li, Hui Zhao, Si-Qi Wang, Newton O Otecko, Dejiu Zhang, Jin-Huan Wang, Yajun Liu, David M Irwin, Yan Qin, Ya-Ping Zhang
Abstract
RNA editing is one of the most common RNA level modifications that potentially generate amino acid changes similar to those resulting from genomic nonsynonymous mutations. However, unlike DNA level allele-specific modifications such as DNA methylation, it is currently unknown whether RNA editing displays allele-specificity across tissues and species. Here, we analyzed allele-specific RNA editing in human tissues and from brain tissues of heterozygous mice generated by crosses between divergent mouse strains and found a high proportion of overlap of allele-specific RNA editing sites between different samples. We identified three allele-specific RNA editing sites cause amino acid changes in coding regions of human and mouse genes, whereas their associated SNPs yielded synonymous differences. In vitro cellular experiments confirmed that sequences differing at a synonymous SNP can have differences in a linked allele-specific RNA editing site with nonsynonymous implications. Further, we demonstrate that allele-specific RNA editing is influenced by differences in local RNA secondary structure generated by SNPs. Our study provides new insights towards a better comprehension of the molecular mechanism that link SNPs with human diseases and traits.
附件下载：
Genome wide analyses uncover allele-specific RNA editing in human and mouse, Nucleic Acids Res, 28 Sep 2018
Nucleic Acids Research, 28 September, 2018, DOI: http://dx.doi.org/10.1093/nar/gky613
Genome wide analyses uncover allele-specific RNA editing in human and mouse
Zhong-Yin Zhou, Yue Hu, Aimin Li, Ying-Ju Li, Hui Zhao, Si-Qi Wang, Newton O Otecko, Dejiu Zhang, Jin-Huan Wang, Yajun Liu, David M Irwin, Yan Qin, Ya-Ping Zhang
Abstract
RNA editing is one of the most common RNA level modifications that potentially generate amino acid changes similar to those resulting from genomic nonsynonymous mutations. However, unlike DNA level allele-specific modifications such as DNA methylation, it is currently unknown whether RNA editing displays allele-specificity across tissues and species. Here, we analyzed allele-specific RNA editing in human tissues and from brain tissues of heterozygous mice generated by crosses between divergent mouse strains and found a high proportion of overlap of allele-specific RNA editing sites between different samples. We identified three allele-specific RNA editing sites cause amino acid changes in coding regions of human and mouse genes, whereas their associated SNPs yielded synonymous differences. In vitro cellular experiments confirmed that sequences differing at a synonymous SNP can have differences in a linked allele-specific RNA editing site with nonsynonymous implications. Further, we demonstrate that allele-specific RNA editing is influenced by differences in local RNA secondary structure generated by SNPs. Our study provides new insights towards a better comprehension of the molecular mechanism that link SNPs with human diseases and traits.
文章链接：https://academic.oup.com/nar/article/46/17/8888/5052368#