Standing your ground to exoribonucleases: Function of Flavivirus long non-coding RNAs.
Standing your ground to exoribonucleases: Function of Flavivirus long non-coding RNAs.
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DOI：
10.1016/j.virusres.2015.09.009
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发表时间：
2016-01-02
期刊：
影响因子：
5
通讯作者：
Wilusz J
中科院分区：
文献类型：
--
作者：
Charley PA;Wilusz J
病毒衍生的长非编码RNA（sfRNA）在所有黄病毒科感染中产生。宿主核酸外切酶Xrn 1在病毒RNA结构上停滞以产生这些lncRNA。停滞的Xrn 1也被抑制，导致细胞mRNA稳定性失调。sfRNA用作诱饵以抵消干扰素和RNAi途径的方面。黄病毒lncRNA在复制、细胞病理学和发病机制中起关键作用。黄病毒科的成员（例如，登革热病毒、西尼罗河病毒和丙型肝炎病毒）含有编码大的多蛋白的正义RNA基因组。现在还清楚的是，如果不是所有的话，大多数这些病毒也产生丰富的亚基因组长非编码RNA。这些非编码RNA被称为亚基因组黄病毒RNA（sfRNA）或Xrn 1抗性RNA（xrRNA），是病毒基因组RNA通过细胞核糖核酸外切酶Xrn 1在高度结构化区域停滞而产生的稳定衰变中间体。近年来，这些黄病毒长非编码RNA的几种功能已被揭示。从病毒转录物产生这些sfRNA/xrRNA导致Xrn 1的抑制和细胞mRNA稳定性的失调。丰富的sfRNA还直接用作干扰素和RNA干扰抗病毒途径的重要细胞蛋白调节剂的诱饵。因此，来自黄病毒、肝炎病毒和瘟病毒的长非编码RNA的产生可能破坏先天免疫的各个方面，并且可能直接促成病毒复制、细胞病理学和发病机制。
Viral-derived long non-coding RNAs (sfRNAs) are made in all Flaviviridae infections. The host exonuclease Xrn1 stalls on viral RNA structures to produce these lncRNAs. Stalled Xrn1 is also repressed, leading to dysregulation of cellular mRNA stability. sfRNA serves as a decoy to counteract aspects of the interferon and RNAi pathways. Flaviviral lncRNAs play a key role in replication, cytopathology and pathogenesis. Members of the Flaviviridae (e.g., Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomic flavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis.