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首页> 外文期刊>Molecular and Cellular Biology >lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta
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lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta

机译:lncRHOXF1,来自X染色体的长非编码RNA,在人类早期胎盘发育过程中抑制病毒反应基因

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Long noncoding RNAs (lncRNAs) can regulate gene expression in a cell-specific fashion during development. Here, we identify a novel lncRNA from the X chromosome that we named lncRHOXF1 and which is abundantly expressed in trophectoderm and primitive endoderm cells of human blastocyst-stage embryos. lncRHOXF1 is a spliced and polyadenylated lncRNA about 1 kb in length that is found in both the nuclear and cytoplasmic compartments of in vitro differentiated human trophectoderm progenitor cells. Gain-of-function experiments in human embryonic stem cells, which normally lack lncRHOXF1 RNA, revealed that lncRHOXF1 reduced proliferation and favored cellular differentiation. lncRHOXF1 knockdown using small interfering RNAs (siRNAs) in human trophectoderm progenitors increased expression of viral response genes, including type I interferon. Sendai virus infection of human trophectoderm progenitor cells increased lncRHOXF1 RNA levels, and siRNA-mediated disruption of lncRHOXF1 during infection reduced the expression of viral response genes leading to higher virus replication. Thus, lncRHOXF1 RNA is the first example of a lncRNA that regulates the host response to viral infections in human placental progenitor cells, and we propose that it functions as a repressor of the viral response during early human development.
机译:长的非编码RNA(lncRNA)可以在发育过程中以细胞特异性方式调节基因表达。在这里,我们从X染色体上鉴定了一个新的lncRNA,我们将其命名为lncRHOXF1,并在人胚泡期胚胎的滋养外胚层和原始内胚层细胞中大量表达。 lncRHOXF1是一个剪接的,聚腺苷酸化的lncRNA,长约1 kb,可在体外分化的人类滋养外胚层祖细胞的核室和细胞质室中找到。在通常缺乏lncRHOXF1 RNA的人胚胎干细胞中进行的功能获得实验显示,lncRHOXF1减少增殖并促进细胞分化。在人类滋养外胚层祖细胞中使用小分子干扰RNA(siRNA)进行 IncRHOXF1 敲低可增加病毒应答基因(包括I型干扰素)的表达。人滋养外胚层祖细胞的仙台病毒感染会增加lncRHOXF1 RNA水平,并且在感染过程中siRNA介导的lncRHOXF1破坏会降低病毒反应基因的表达,从而导致更高的病毒复制。因此,lncRHOXF1 RNA是调控宿主对人胎盘祖细胞中病毒感染的应答的lncRNA的第一个实例,我们建议其在人类早期发育过程中起病毒应答的阻遏作用。

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