Department of Molecular Biology, Aarhus University, C. F. Møllers Allé 3, Denmark.
Nucleic Acids Res. 2011 May;39(9):3754-70. doi: 10.1093/nar/gkq1282. Epub 2011 Jan 17.
The vertebrate 2-5A system is part of the innate immune system and central to cellular antiviral defense. Upon activation by viral double-stranded RNA, 5'-triphosphorylated, 2'-5'-linked oligoadenylate polyribonucleotides (2-5As) are synthesized by one of several 2'-5'-oligoadenylate synthetases. These unusual oligonucleotides activate RNase L, an unspecific endoribonuclease that mediates viral and cellular RNA breakdown. Subsequently, the 2-5As are removed by a 2'-phosphodiesterase (2'-PDE), an enzyme that apart from breaking 2'-5' bonds also degrades regular, 3'-5'-linked oligoadenylates. Interestingly, 2'-PDE shares both functionally and structurally characteristics with the CCR4-type exonuclease-endonuclease-phosphatase family of deadenylases. Here we show that 2'-PDE locates to the mitochondrial matrix of human cells, and comprise an active 3'-5' exoribonuclease exhibiting a preference for oligo-adenosine RNA like canonical cytoplasmic deadenylases. Furthermore, we document a marked negative association between 2'-PDE and mitochondrial mRNA levels following siRNA-directed knockdown and plasmid-mediated overexpression, respectively. The results indicate that 2'-PDE, apart from playing a role in the cellular immune system, may also function in mitochondrial RNA turnover.
脊椎动物 2-5A 系统是先天免疫系统的一部分，也是细胞抗病毒防御的核心。在病毒双链 RNA 激活后，由几种 2′-5′寡聚腺苷酸合成酶之一合成 5′-三磷酸化、2′-5′-连接的寡聚腺苷酸多核苷酸（2-5As）。这些不寻常的寡核苷酸激活 RNA 酶 L，一种非特异性内切核糖核酸酶，介导病毒和细胞 RNA 的分解。随后，2′-磷酸二酯酶（2′-PDE）将 2-5As 去除，该酶除了切断 2′-5′键外，还降解常规的 3′-5′连接寡腺苷酸。有趣的是，2′-PDE 在功能和结构上都与 CCR4 型外切核酸酶-内切核酸酶-磷酸酶家族的脱腺苷酶具有相似性。在这里，我们表明 2′-PDE 位于人细胞的线粒体基质中，并且构成具有活性的 3′-5′外切核糖核酸酶，对寡腺苷酸 RNA 表现出与经典细胞质脱腺苷酶相似的偏好。此外，我们记录了在 siRNA 介导的敲低和质粒介导的过表达后，2′-PDE 与线粒体 mRNA 水平之间存在明显的负相关。结果表明，2′-PDE 除了在细胞免疫系统中发挥作用外，还可能在线粒体 RNA 周转中发挥作用。
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