TY - JOUR T1 - Unbiased identification of <em>trans</em> regulators of ADAR and A-to-I RNA editing JF - bioRxiv DO - 10.1101/631200 SP - 631200 AU - Emily C. Freund AU - Anne L. Sapiro AU - Qin Li AU - Sandra Linder AU - James J. Moresco AU - John R. Yates III AU - Jin Billy Li Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/08/631200.1.abstract N2 - Adenosine-to-Inosine RNA editing is catalyzed by ADAR enzymes that deaminate adenosine to inosine. While many RNA editing sites are known, few trans regulators have been identified. We perform BioID followed by mass-spectrometry to identify trans regulators of ADAR1 and ADAR2 in HeLa and M17 neuroblastoma cells. We identify known and novel ADAR-interacting proteins. Using ENCODE data we validate and characterize a subset of the novel interactors as global or site-specific RNA editing regulators. Our set of novel trans regulators includes all four members of the DZF-domain-containing family of proteins: ILF3, ILF2, STRBP, and ZFR. We show that these proteins interact with each ADAR and modulate RNA editing levels. We find ILF3 is a global negative regulator of editing. This work demonstrates the broad roles RNA binding proteins play in regulating editing levels and establishes DZF-domain containing proteins as a group of highly influential RNA editing regulators. ER -