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

Giovanni Quinones-Valdez(University of California, Los Angeles), Stephen Tran(University of California, Los Angeles), Hyun-Ik Jun(University of California, Los Angeles), Jae Hoon Bahn(University of California, Los Angeles), Ei-Wen Yang(University of California, Los Angeles), Lijun Zhan(Institute for Systems Biology), Anneke Brümmer(University of California, Los Angeles), Xintao Wei(Institute for Systems Biology), Eric L. Van Nostrand(University of California San Diego), Henry Pratt(University of California San Diego), G Yeo(University of California San Diego), Brenton R. Graveley(Institute for Systems Biology), Xinshu Xiao(QB3)
Communications Biology
January 8, 2019
10.1038/s42003-018-0271-8
Cited by 154Open Access
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Abstract

Abstract 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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