Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules.
Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules.
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DOI：
10.1093/nar/gkt750
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发表时间：
2013-11
影响因子：
14.9
通讯作者：
Scadden AD
中科院分区：
文献类型：
--
作者：
Ng SK;Weissbach R;Ronson GE;Scadden AD
长的双链RNA可以通过作用于RNA的腺苷脱氨酶（ADAR）进行超编辑，其中高达50%的腺苷残基可以转化为肌苷。然而，尽管许多RNA可能经历超编辑，但对细胞中含有肌苷的超编辑双链RNA的作用知之甚少。然而，编辑在哺乳动物细胞中起着关键作用，正如ADAR无效突变体的分析所强调的那样。特别是，ADAR 1的长型（ADAR 1 p150）对于生存力至关重要。此外，许多研究表明ADAR 1 p150参与了各种应激途径。我们以前已经表明，ADAR 1 p150定位于细胞质的压力颗粒在HeLa细胞后，无论是氧化或干扰素诱导的压力。在这里，我们表明，Z-DNA结合结构域（Zα ADAR 1）只在ADAR 1 p150中发现，是其定位到应激颗粒所必需的。此外，我们发现Zα ADAR 1与绿色荧光蛋白（GFP）或多聚嘧啶结合蛋白4（PTB 4）的融合也导致它们定位于应激颗粒。我们还表明，来自其他Z-DNA结合蛋白（ZBP 1，E3 L）的Zα结构域同样足以定位于应激颗粒。最后，我们表明，Z-RNA或Z-DNA结合是重要的压力颗粒定位。因此，我们已经确定了哺乳动物细胞中的Z-DNA结合结构域的一个新的作用。
Long double-stranded RNA may undergo hyper-editing by adenosine deaminases that act on RNA (ADARs), where up to 50% of adenosine residues may be converted to inosine. However, although numerous RNAs may undergo hyper-editing, the role for inosine-containing hyper-edited double-stranded RNA in cells is poorly understood. Nevertheless, editing plays a critical role in mammalian cells, as highlighted by the analysis of ADAR-null mutants. In particular, the long form of ADAR1 (ADAR1p150) is essential for viability. Moreover, a number of studies have implicated ADAR1p150 in various stress pathways. We have previously shown that ADAR1p150 localized to cytoplasmic stress granules in HeLa cells following either oxidative or interferon-induced stress. Here, we show that the Z-DNA-binding domain (ZαADAR1) exclusively found in ADAR1p150 is required for its localization to stress granules. Moreover, we show that fusion of ZαADAR1 to either green fluorescent protein (GFP) or polypyrimidine binding protein 4 (PTB4) also results in their localization to stress granules. We additionally show that the Zα domain from other Z-DNA-binding proteins (ZBP1, E3L) is likewise sufficient for localization to stress granules. Finally, we show that Z-RNA or Z-DNA binding is important for stress granule localization. We have thus identified a novel role for Z-DNA-binding domains in mammalian cells.
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DOI：
10.1073/pnas.240464097
发表时间：
2000-12-05
影响因子：
11.1
作者：
Brown, BA;Lowenhaupt, K;Rich, A
通讯作者：
Rich, A
影响因子：
4
作者：
Desterro, JMP;Keegan, LR;Carmo-Fonseca, M
通讯作者：
Carmo-Fonseca, M
影响因子：
14.9
作者：
Deigendesch, Nikolaus;Koch-Nolte, Friedrich;Rothenburg, Stefan
通讯作者：
Rothenburg, Stefan
影响因子：
7
作者：
Blow, M;Futreal, PA;Stratton, MR
通讯作者：
Stratton, MR
影响因子：
5.6
作者：
Athanasiadis, A;Placido, D;Rich, A
通讯作者：
Rich, A