bioRxiv preprint doi: https://doi.org/10.1101/631200; this version posted May 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Unbiased identification of trans regulators of ADAR and A-to-I RNA editing 2 3 Emily C. Freund1, Anne L. Sapiro1, Qin Li1, Sandra Linder1, James J. Moresco2, John R. Yates 4 III2, Jin Billy Li1 5 6 1 Department of Genetics, Stanford University, Stanford, CA, USA 7 2 Department of Molecular Medicine, 10550 North Torrey Pines Road, SR302, The Scripps 8 Research Institute, La Jolla, California 92037 9 10 Correspondence:
[email protected] 11 12 13 Abstract 14 Adenosine-to-Inosine RNA editing is catalyzed by ADAR enzymes that deaminate adenosine to 15 inosine. While many RNA editing sites are known, few trans regulators have been identified. We 16 perform BioID followed by mass-spectrometry to identify trans regulators of ADAR1 and ADAR2 17 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. 18 Using ENCODE data we validate and characterize a subset of the novel interactors as global or 19 site-specific RNA editing regulators. Our set of novel trans regulators includes all four members 20 of the DZF-domain-containing family of proteins: ILF3, ILF2, STRBP, and ZFR. We show that 21 these proteins interact with each ADAR and modulate RNA editing levels.