ADAR Regulates RNA Editing, Transcript Stability, and Gene Expression

被引:156
作者
Wang, Isabel X. [2 ]
So, Elizabeth [2 ]
Devlin, James L. [2 ]
Zhao, Yue [1 ]
Wu, Ming [1 ]
Cheung, Vivian G. [1 ,2 ,3 ]
机构
[1] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
[2] Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Pediat, Sch Med, Philadelphia, PA 19104 USA
来源
CELL REPORTS | 2013年 / 5卷 / 03期
基金
美国国家卫生研究院;
关键词
DOUBLE-STRANDED-RNA; BINDING PROTEIN HUR; MESSENGER-RNA; ADENOSINE-DEAMINASE; WIDESPREAD RNA; PARALLEL DNA; IN-VITRO; IDENTIFICATION; SITES; DETERMINANTS;
D O I
10.1016/j.celrep.2013.10.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine, which is then recognized as guanosine. To study the role of ADAR proteins in RNA editing and gene regulation, we sequenced and compared the DNA and RNA of human B cells. Then, we followed up the findings experimentally with siRNA knockdown and RNA and protein immunoprecipitations. The results uncovered over 60,000 A-to-G editing sites and several thousand genes whose expression levels are influenced by ADARs. Of these ADAR targets, 90% were identified. Our results also reveal that ADAR regulates transcript stability and gene expression through interaction with HuR (ELAVL1). These findings extend the role of ADAR and show that it cooperates with other RNA-processing proteins to regulate the sequence and expression of transcripts in human cells.
引用
收藏
页码:849 / 860
页数:12
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