Abstract
Nuclear paraspeckle assembly transcript 1 (NEAT1) is the crucial structural platform of paraspeckles, which is one type of nuclear bodies. As a stress-induced lncRNA, the expression of NEAT1 increases in response to viral infection, but little is known about the role of NEAT1 or paraspeckles in the replication of herpes simplex virus-1 (HSV-1). Here, we demonstrate that HSV-1 infection increases NEAT1 expression and paraspeckle formation in a STAT3-dependent manner. NEAT1 and other paraspeckle protein components, P54nrb and PSPC1, can associate with HSV-1 genomic DNA. By binding with STAT3, PSPC1 is required for the recruitment of STAT3 to paraspeckles and facilitates the interaction between STAT3 and viral gene promoters, finally increasing viral gene expression and viral replication. Furthermore, thermosensitive gel containing NEAT1 siRNA or STAT3 siRNA effectively healed the skin lesions caused by HSV-1 infection in mice. Our results provide insight into the roles of lncRNAs in the epigenetic control of viral genes and into the function of paraspeckles.
Highlights
IntroductionNuclear paraspeckle assembly transcript 1 (NEAT1), a long noncoding RNA (lncRNA) in animal cells, exists in two isoforms: NEAT1v1 (human 3.7 kb; mouse 3.2 kb) and NEAT1v2 (human 22.7 kb; mouse 20 kb)
Nuclear paraspeckle assembly transcript 1 (NEAT1), a long noncoding RNA in animal cells, exists in two isoforms: NEAT1v1 and NEAT1v2
Using an RNA fluorescence in situ hybridization (FISH) assay, we found that herpes simplex virus-1 (HSV-1) infection increases the number of NEAT1 puncta (Fig. 1c), suggesting that viral infection induces the formation of paraspeckles, possibly by increasing the expression of NEAT1, which is the organizer of paraspeckles
Summary
NEAT1, a long noncoding RNA (lncRNA) in animal cells, exists in two isoforms: NEAT1v1 (human 3.7 kb; mouse 3.2 kb) and NEAT1v2 (human 22.7 kb; mouse 20 kb). Previous studies have reported the cellular functions of NEAT1, including its function in the retention of inverted Alu repeat-containing RNAs in paraspeckle-associated complexes [1] and its regulation of gene expression by binding to active chromatin sites [2]. NEAT1 has been shown to provide a crucial structural framework for organizing paraspeckles, which are recently discovered nuclear bodies in mammalian cells with unclear functions [3, 4]. Paraspeckles are found in the nuclei of mammalian cells and are formed by lncRNA and numerous RNA-binding proteins [5]. Some functions of the paraspeckle components have been examined, few reports have focused on the functions of paraspeckles as nuclear bodies. The potential functions of paraspeckles include the transcriptional regulation of gene expression by retaining mRNAs in the nucleus [11] and the sequestration of transcription factors from the promoters of target genes [12, 13]
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