Regulation of RNA editing by RNA-binding proteins in human cells

被引:92
作者
Quinones-Valdez, Giovanni [1 ]
Tran, Stephen S. [2 ]
Jun, Hyun-Ik [3 ]
Bahn, Jae Hoon [3 ]
Yang, Ei-Wen [3 ]
Zhan, Lijun [4 ]
Brummer, Anneke [3 ]
Wei, Xintao [4 ]
Van Nostrand, Eric L. [5 ,6 ]
Pratt, Gabriel A. [5 ,6 ,7 ]
Yeo, Gene W. [5 ,6 ,7 ]
Graveley, Brenton R. [4 ]
Xiao, Xinshu [1 ,2 ,3 ,8 ,9 ]
机构
[1] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA 90095 USA
[4] UConn Hlth, Dept Genet & Genome Sci, Inst Syst Genom, Farmington, CT 06030 USA
[5] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA
[6] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA
[7] Univ Calif San Diego, Bioinformat & Syst Biol Grad Program, La Jolla, CA 92093 USA
[8] Univ Calif Los Angeles, Mol Biol Inst, Los Angeles, CA 90095 USA
[9] Univ Calif Los Angeles, Inst Quantitat & Computat Biol, Los Angeles, CA 90095 USA
关键词
TRANSCRIPTOME-WIDE DISCOVERY; MESSENGER-RNAS; DSRNA BINDING; COMPLEX; DATABASE; DISEASE; ROLES; IDENTIFICATION; SUBUNIT; NF90;
D O I
10.1038/s42003-018-0271-8
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Adenosine-to-inosine (A-to-I) editing, mediated by the ADAR enzymes, diversifies the transcriptome by altering RNA sequences. Recent studies reported global changes in RNA editing in disease and development. Such widespread editing variations necessitate an improved understanding of the regulatory mechanisms of RNA editing. Here, we study the roles of >200 RNA-binding proteins (RBPs) in mediating RNA editing in two human cell lines. Using RNA-sequencing and global protein-RNA binding data, we identify a number of RBPs as key regulators of A-to-I editing. These RBPs, such as TDP-43, DROSHA, NF45/90 and Ro60, mediate editing through various mechanisms including regulation of ADAR1 expression, interaction with ADAR1, and binding to Alu elements. We highlight that editing regulation by Ro60 is consistent with the global up-regulation of RNA editing in systemic lupus erythematosus. Additionally, most key editing regulators act in a cell type-specific manner. Together, our work provides insights for the regulatory mechanisms of RNA editing.
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页数:14
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