Functional prediction of differentially expressed lncRNAs in HSV-1 infected human foreskin fibroblasts.

Functional prediction of differentially expressed lncRNAs in HSV-1 infected human foreskin fibroblasts.
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HSV-1感染的人包皮成纤维细胞中差异表达的lncRNA的功能预测

DOI:
10.1186/s12985-016-0592-5
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发表时间:
2016-08-05
期刊:
影响因子:
4.8
通讯作者:
Zhou J
Zhou J
中科院分区:
医学3区
文献类型:
--
作者:
Hu B;Huo Y;Chen G;Yang L;Wu D;Zhou J

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长链非编码RNA(longnoncodingRNA,lncRNA)的最重要功能之一是通过局部顺式或远程反式作用来控制蛋白质编码基因的转录。单纯疱疹病毒I型(HerpesSimplexVirus type I,HSV-1)潜伏感染超过80%的人群,其从潜伏期的再激活通常导致人类上皮细胞的生产性感染,并且是常见的唇疱疹和生殖器疱疹的原因。HSV-1生产性感染导致宿主细胞的深刻变化,包括宿主转录组。然而,全基因组lncRNA表达如何受到感染的影响以及lncRNA表达如何与蛋白质编码基因表达相关尚未分析。我们从HSV-1感染的人包皮成纤维细胞(HFF)中的RNA-seq数据分析了差异表达的lncRNA及其潜在靶点。基于差异表达的蛋白质编码基因与lncRNA表达模式的相关性,我们预测这些lncRNA可能以顺式或反式调节许多细胞蛋白质编码基因的表达。本文分析了HSV-1感染诱导的差异表达lncRNA,并预测了其靶基因。我们检测到208个注释和206个新的差异表达的lncRNA。基因本体和途径富集分析揭示了潜在的lncRNA靶点,包括染色质组装中的基因、神经元发育和神经退行性疾病中的基因以及免疫应答中的基因,例如Toll样受体信号传导和RIG-I样受体信号传导途径。我们发现,差异表达的lncRNA可以调节参与从天然免疫到神经元发育的途径的许多细胞蛋白编码基因的表达,从而揭示了lncRNA在HSV-1感染的人细胞中调节宿主转录程序的重要作用。本文的在线版本(doi:10.1186/s12985 - 016 - 0592 - 5)包含补充材料,可供授权用户使用。
One of the most important functions of long noncoding RNAs (lncRNAs) is to control protein coding gene transcription by acting locally in cis, or remotely in trans. Herpes Simplex Virus type I (HSV-1) latently infects over 80 % of the population, its reactivation from latency usually results in productive infections in human epithelial cells, and is responsible for the common cold sores and genital Herpes. HSV-1 productive infection leads to profound changes in the host cells, including the host transcriptome. However, how genome wide lncRNAs expressions are affected by the infection and how lncRNAs expression relates to protein coding gene expression have not been analyzed. We analyzed differentially expressed lncRNAs and their potential targets from RNA-seq data in HSV-1 infected human foreskin fibroblast (HFF) cells. Based on correlations of expression patterns of differentially expressed protein-coding genes and lncRNAs, we predicted that these lncRNAs may regulate, either in cis or in trans, the expression of many cellular protein-coding genes. Here we analyzed HSV-1 infection induced, differentially expressed lncRNAs and predicted their target genes. We detected 208 annotated and 206 novel differentially expressed lncRNAs. Gene Ontology and Pathway enrichment analyses revealed potential lncRNA targets, including genes in chromatin assembly, genes in neuronal development and neurodegenerative diseases and genes in the immune response, such as Toll-like receptor signaling and RIG-I-like receptor signaling pathways. We found that differentially expressed lncRNAs may regulate the expression of many cellular protein-coding genes involved in pathways from native immunity to neuronal development, thus revealing important roles of lncRNAs in the regulation of host transcriptional programs in HSV-1 infected human cells. The online version of this article (doi:10.1186/s12985-016-0592-5) contains supplementary material, which is available to authorized users.