STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1.
STAT2-dependent induction of RNA adenosine deaminase ADAR1 by type I interferon differs between mouse and human cells in the requirement for STAT1.
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DOI：
10.1016/j.virol.2015.08.001
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发表时间：
2015-11
期刊：
影响因子：
3.7
通讯作者：
Samuel CE
中科院分区：
文献类型：
--
作者：
George CX;Samuel CE
作用于RNA1的腺苷脱氨酶（ADAR1）的表达是由替代启动子驱动的。由干扰素（IFN）激活的启动子PA产生编码可诱导的p150 ADAR1蛋白的转录本，而PB则指定组成表达的p110蛋白。我们使用Stat1−/−、Stat2−/−和IRF9−/−mef表明，ADAR1 p150的诱导是通过Stat2 -和IRF9依赖性信号发生的，这种信号被Stat1增强，但不是强制性地依赖于Stat1。染色质免疫沉淀分析显示，在ifn处理的Stat1−/−细胞中，PA启动子上有STAT2，而ifn处理的野生型细胞中，PA启动子上同时存在Stat1和STAT2。相比之下，在人2fTGH细胞和突变体U3A或U6A中，IFN诱导ADAR1同时依赖于STAT1和STAT2。这些结果表明，在没有STAT1的情况下，IFN通过非典型的stat2依赖性途径激活Adar1，但在小鼠细胞中不存在。
Expression of adenosine deaminase acting on RNA1 (ADAR1) is driven by alternative promoters. Promoter PA, activated by interferon (IFN), produces transcripts that encode the inducible p150 ADAR1 protein, whereas PB specifies the constitutively expressed p110 protein. We show using Stat1−/−, Stat2−/− and IRF9−/− MEFs that induction of ADAR1 p150 occurs by STAT2- and IRF9-dependent signaling that is enhanced by, but not obligatorily dependent upon, STAT1. Chromatin immunoprecipitation analysis demonstrated STAT2 at the PA promoter in IFN-treated Stat1−/− cells, whereas IFN-treated wild-type cells showed both STAT1 and STAT2 bound at PA. By contrast, with human 2fTGH cells and mutants U3A or U6A, ADAR1 induction by IFN was dependent upon both STAT1 and STAT2. These results suggest that transcriptional activation of Adar1 by IFN occurs in the absence of STAT1 by a non-canonical STAT2-dependent pathway in mouse but not human cells.