ADAR1 interacts with NF90 through double-stranded RNA and regulates NF90-mediated gene expression independently of RNA editing
ADAR1 interacts with NF90 through double-stranded RNA and regulates NF90-mediated gene expression independently of RNA editing
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DOI：
10.1128/mcb.25.16.6956-6963.2005
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发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Yang, JH
中科院分区：
文献类型：
--
作者：
Nie, YZ;Ding, L;Yang, JH
RNA编辑酶ADAR 1通过脱氨基作用修饰腺苷，并在mRNA中产生A到1的突变。ADAR 1最近被证明在宿主防御和胎儿肝脏发育期间的胚胎红细胞生成中起作用。这些表型效应的机制尚不清楚。在这里，我们报告了一种新的功能ADAR 1在基因表达的调节，通过与核因子90（NF 90）蛋白，已知的监管机构，结合抗原反应识别元件（ARRE-2），并已被证明刺激转录和翻译的相互作用。ADAR 1通过与NF 90蛋白（包括NF 110、NF 90和NF 45）相互作用上调NF 90介导的基因表达。用小干扰RNA敲低NF 90抑制ADAR 1的这种功能。免疫共沉淀和双链RNA（dsRNA）消化证明ADAR 1通过细胞dsRNA的桥与NF 110、NF 90和NF 45相关联。ADAR 1缺失的研究表明，dsRNA结合结构域和覆盖Z-DNA结合结构域的区域以及核输出信号包含ADAR 1在上调NF 90介导的基因表达中的完整功能。这些数据表明，ADAR 1有可能通过编辑mRNA来改变信息内容，并通过与NF 90家族蛋白相互作用来调节基因表达。
The RNA-editing enzyme ADAR1 modifies adenosines by deamination and produces A-to-1 mutations in mRNA. ADAR1 was recently demonstrated to function in host defense and in embryonic erythropoiesis during fetal liver development. The mechanisms for these phenotypic effects are not yet known. Here we report a novel function of ADAR1 in the regulation of gene expression by interacting with the nuclear factor 90 (NF90) proteins, known regulators that bind the antigen response recognition element (ARRE-2) and have been demonstrated to stimulate transcription and translation. ADAR1 upregulates NF90-mediated gene expression by interacting with the NF90 proteins, including NF110, NF90, and NF45. A knockdown of NF90 with small interfering RNA suppresses this function of ADAR1. Coimmunoprecipitation and double-stranded RNA (dsRNA) digestion demonstrate that ADAR1 is associated with NF110, NF90, and NF45 through the bridge of cellular dsRNA. Studies with ADAR1 deletions demonstrate that the dsRNA binding domain and a region covering the Z-DNA binding domain and the nuclear export signal comprise the complete function of ADAR1 in upregulating NF90-mediated gene expression. These data suggest that ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins.