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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation
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Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation

机译:严重急性呼吸系统综合症冠状病毒nsp1蛋白通过促进宿主mRNA降解抑制宿主基因表达

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摘要

Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5' end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-beta mRNA accumulation without inhibiting climerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-beta promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.
机译:严重急性呼吸系统综合症(SARS)冠状病毒(SCoV)引起与肺炎有关的新近出现的人类疾病。单链正义病毒基因组RNA基因1的三分之二的5'端编码16种成熟蛋白。 Nsp1是N端基因1最多的蛋白,它的表达阻止了仙台病毒诱导的内源性IFN-βmRNA的积累,而没有抑制IFN调节因子3的老化,而IFN调节因子3对于激活IFN-β启动子至关重要。此外,nsp1表达促进表达的RNA转录物和宿主内源性mRNA的降解,从而导致强烈的宿主蛋白合成抑制作用。 SCoV复制还促进表达的RNA转录物和宿主mRNA的降解,这表明nsp1在感染细胞中发挥了其mRNA不稳定功能。与nsp1诱导的mRNA稳定化相反,在表达nsp1的细胞或SCoV感染的细胞中,28S和18S rRNA均未发生降解。这些数据表明,在被感染的细胞中,nsp1促进宿主mRNA降解,从而抑制宿主基因表达,包括参与宿主先天免疫功能的蛋白质。 SCoV nsp1介导的宿主mRNA降解的促进可能在SCoV发病机理中起重要作用。

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