Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Department of Molecular Medicine, 10550 North Torrey Pines Road, SR302, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell Rep. 2020 May 19;31(7):107656. doi: 10.1016/j.celrep.2020.107656.
Adenosine-to-inosine RNA editing is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes that deaminate adenosine to inosine. Although 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 broadly influential negative regulator of editing. This work demonstrates the broad roles that RNA binding proteins play in regulating editing levels, and establishes DZF-domain-containing proteins as a group of highly influential RNA editing regulators.
腺嘌呤核苷到肌苷核苷 RNA 编辑是由腺嘌呤脱氨酶作用于 RNA（ADAR）酶催化的，该酶将腺嘌呤脱氨成肌苷。尽管已经知道许多 RNA 编辑位点，但很少有鉴定出的转录调节因子。我们在 HeLa 和 M17 神经母细胞瘤细胞中进行 BioID 实验，随后进行质谱分析，以鉴定 ADAR1 和 ADAR2 的转录调节因子。我们鉴定出已知和新的 ADAR 相互作用蛋白。使用 ENCODE 数据，我们验证和表征了新相互作用蛋白的子集，作为全局或特定位点 RNA 编辑调节因子。我们的一组新的转录调节因子包括 DZF 结构域蛋白家族的所有四个成员：ILF3、ILF2、STRBP 和 ZFR。我们表明这些蛋白与每个 ADAR 相互作用，并调节 RNA 编辑水平。我们发现 ILF3 是一种广泛影响编辑的负调节因子。这项工作表明 RNA 结合蛋白在调节编辑水平方面发挥着广泛的作用，并确立了 DZF 结构域蛋白作为一组具有高度影响力的 RNA 编辑调节因子。
