Abstract
BackgroundOne 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.MethodsWe 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.ResultsHere 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0592-5) contains supplementary material, which is available to authorized users.
Highlights
One of the most important functions of long noncoding RNAs is to control protein coding gene transcription by acting locally in cis, or remotely in trans
LncRNAs expressed in herpes simplex virus type i (HSV-1) infected human foreskin fibroblast (HFF) cells To determine how long noncoding RNA (lncRNA) expression is affected by HSV-1 infection, we analyzed RNA-seq datasets from NCBI Gene Expression Omnibus (GEO) and filtered the low quality reads using FASTX-Toolkit software, followed by aligning RNA-seq data onto human reference genome with Tophat2 [37], and subsequently using Cufflinks [38] and Cuffcompare [38] to assemble and compare transcripts
We found genes positively affected by lncRNAs through in trans were enriched in B cell receptor signaling pathway, which resulted in the expression of immediate early genes that further activated the expression of other genes involved in B cell proliferation, differentiation and Ig production as well as other processes [61]
Summary
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. How genome wide lncRNAs expressions are affected by the infection and how lncRNAs expression relates to protein coding gene expression have not been analyzed. LncRNA is implicated in tumorigenesis, for example, a lncRNA ceruloplasmin (NRCP) was highly up-regulated in ovarian tumors, which significantly increased cancer cell growth by altering glycolysis compared with normal cells [9]. LncRNA is implicated in pathogen-host interaction [11], for example, a cellular lncRNA, negative regulator of antiviral response (NRAV), promoted influenza A virus (IAV) replication and virulence
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