Unbiased Identification of trans Regulators of ADAR and A-to-I RNA Editing.,Cell Reports

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Unbiased Identification of trans Regulators of ADAR and A-to-I RNA Editing.
Cell Reports ( IF 7.5 ) Pub Date : 2020-05-19 , DOI: 10.1016/j.celrep.2020.107656
Emily C Freund ₁ , Anne L Sapiro ₁ , Qin Li ₁ , Sandra Linder ₁ , James J Moresco ₂ , John R Yates ₂ , Jin Billy Li ₁

Affiliation

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.

中文翻译：

ADAR反式调节子的无偏鉴定和A-to-I RNA编辑。

腺苷到肌苷的RNA编辑是通过作用于将腺苷脱氨为肌苷的RNA（ADAR）酶上的腺苷脱氨酶来催化的。尽管已知许多RNA编辑位点，但几乎未发现反式调节子。我们执行BioID，然后进行质谱分析，以鉴定HeLa和M17神经母细胞瘤细胞中ADAR1和ADAR2的反式调节子。我们确定已知和新型的ADAR相互作用蛋白。使用ENCODE数据，我们验证并将新型相互作用子的一个子集表征为全局或位点特定的RNA编辑调节剂。我们的一组新颖的反式调节剂包括DZF结构域蛋白家族的所有四个成员：ILF3，ILF2，STRBP和ZFR。我们显示这些蛋白质与每个ADAR相互作用并调节RNA编辑水平。我们发现ILF3是广泛影响编辑的负面调节器。

更新日期：2020-05-19

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