title: Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules.
abstract: 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 (ADAR1(p150)) is essential for viability. Moreover, a number of studies have implicated ADAR1(p150) in various stress pathways. We have previously shown that ADAR1(p150) localized to cytoplasmic stress granules in HeLa cells following either oxidative or interferon-induced stress. Here, we show that the Z-DNA-binding domain (Zα(ADAR1)) exclusively found in ADAR1(p150) is required for its localization to stress granules. Moreover, we show that fusion of Zα(ADAR1) 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.
authors: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
authors: Siew Kit
authors: SK
authors: Ng
authors: Rebekka
authors: R
authors: Weissbach
authors: George E
authors: GE
authors: Ronson
authors: A D J
authors: AD
authors: Scadden
mesh_terms: D000243:Adenosine Deaminase / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry; D003594:Cytoplasmic Granules / Q000201:enzymology*; D043542:DNA, Z-Form / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000737:chemistry; D018384:Oxidative Stress; D011070:Poly I-C / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins; D014764:Viral Proteins / Q000032:analysis / Q000737:chemistry
chemical_list: D000596:Amino Acids; D043542:DNA, Z-Form; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D011070:Poly I-C
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