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Commun Biol. 2019 Jan 14;2:19. doi: 10.1038/s42003-018-0271-8. eCollection 2019.

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

Author information

1
1Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095 USA.
2
2Bioinformatics Interdepartmental Program, University of California Los Angeles, Los Angeles, CA 90095 USA.
3
3Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA 90095 USA.
4
4Department of Genetics and Genome Sciences, Institute for Systems Genomics, UConn Health, Farmington, CT 06030 USA.
5
5Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093 USA.
6
6Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093 USA.
7
7Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093 USA.
8
8Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA 90095 USA.
9
9Institute for Quantitative and Computational Biology, University of California Los Angeles, Los Angeles, CA 90095 USA.

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.

Conflict of interest statement

G.W.Y. is a co-founder of Locana and Eclipse Bioinnovations and member of the scientific advisory boards of Locana, Eclipse Bioinnovations and Aquinnah Pharmaceuticals. E.V.N is a co-founder and member of the scientific advisory board of Eclipse BioInnovations. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. The remaining authors declare no competing interests.

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