A role for H/ACA and C/D small nucleolar RNAs in viral replication.

A role for H/ACA and C/D small nucleolar RNAs in viral replication.
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H/ACA和C/D小核仁RNA在病毒复制中的作用。

DOI:
10.1007/s12033-013-9730-0
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发表时间:
2014-05
影响因子:
2.6
通讯作者:
Rubin DH
Rubin DH
中科院分区:
医学4区
文献类型:
--
作者:
Murray JL;Sheng J;Rubin DH

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在使用 12 种不同病毒和几种不同细胞系的独立研究中,我们采用基因陷阱插入诱变来鉴定候选基因,这些基因的破坏赋予对裂解感染的表型抗性。对超过 2,000 个抗病毒克隆的分析揭示了超过 1,000 个候选宿主基因,其中约 20% 在分别感染 2-6 种病毒后幸存的克隆中被破坏。有趣的是,有 83 个实例中插入诱变载体破坏了编码 H/ACA 类和 C/D 类小核仁 RNA(分别为 SNORAs 和 SNORD)的转录本。其中,79 个 SNORA 和 SNORD 位于 29 个基因(主要编码蛋白质)的内含子内,而 4 个似乎是独立的转录单位。针对候选 SNORA/D 的 siRNA 研究在针对牛痘病毒、登革热病毒、甲型流感病毒、人鼻病毒 16、单纯疱疹病毒 2 或呼吸道合胞病毒进行测试时,独立证实了它们在感染中的作用。值得注意的是,9 个 SNORA/D 中的 8 个以 siRNA 为靶点,增强了细胞对多种病毒的抵抗力,表明 SNORA/D 广泛参与病毒与宿主相互作用和/或病毒诱导的细胞死亡。
We have employed gene-trap insertional mutagenesis to identify candidate genes whose disruption confer phenotypic resistance to lytic infection, in independent studies using 12 distinct viruses and several different cell lines. Analysis of >2,000 virus-resistant clones revealed >1,000 candidate host genes, approximately 20 % of which were disrupted in clones surviving separate infections with 2–6 viruses. Interestingly, there were 83 instances in which the insertional mutagenesis vector disrupted transcripts encoding H/ACA-class and C/D-class small nucleolar RNAs (SNORAs and SNORDs, respectively). Of these, 79 SNORAs and SNORDs reside within introns of 29 genes (predominantly protein-coding), while 4 appear to be independent transcription units. siRNA studies targeting candidate SNORA/Ds provided independent confirmation of their roles in infection when tested against cowpox virus, Dengue Fever virus, influenza A virus, human rhinovirus 16, herpes simplex virus 2, or respiratory syncytial virus. Significantly, eight of the nine SNORA/Ds targeted with siRNAs enhanced cellular resistance to multiple viruses suggesting widespread involvement of SNORA/Ds in virus–host interactions and/or virus-induced cell death.
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