Speckles and paraspeckles coordinate to regulate HSV-1 genes transcription

Kun Li,Ziqiang Wang

doi:10.1038/s42003-021-02742-6

Abstract

Numbers of nuclear speckles and paraspeckles components have been demonstrated to regulate herpes simplex virus 1 (HSV-1) replication. However, how HSV-1 infection affects the two nuclear bodies, and whether this influence facilitates the expression of viral genes, remains elusive. In the current study, we found that HSV-1 infection leads to a redistribution of speckles and paraspeckles components. Serine/arginine-rich splicing factor 2 (SRSF2), the core component of speckles, was associated with multiple paraspeckles components, including nuclear paraspeckles assembly transcript 1 (NEAT1), PSPC1, and P54nrb, in HSV-1 infected cells. This association coordinates the transcription of viral genes by binding to the promoters of these genes. By association with the enhancer of zeste homolog 2 (EZH2) and P300/CBP complex, NEAT1 and SRSF2 influenced the histone modifications located near viral genes. This study elucidates the interplay between speckles and paraspeckles following HSV-1 infection and provides insight into the mechanisms by which HSV-1 utilizes host cellular nuclear bodies to facilitate its life cycle.

Highlights

Numbers of nuclear speckles and paraspeckles components have been demonstrated to regulate herpes simplex virus 1 (HSV-1) replication
Given that the speckles and paraspeckles are two adjacent subcellular organelles in a special location and the component of speckles, and Serine/arginine-rich splicing factor 2 (SRSF2), the components of paraspeckles, nuclear paraspeckles assembly transcript 1 (NEAT1), PSPC1, and P54nrb, function as transcriptional activators for HSV-1 genes expression reported by our previous studies[21,22], we hypothesized that the components of the speckles and paraspeckles work together to modulate viral genes transcription under HSV-1 infection conditions
In order to determine whether HSV-1 infection resulted in a reorganization of these components, we first confirmed the infection efficiency of HSV-1 in HeLa cells (Supplementary Fig. 1a) and C-33A cells (Supplementary Fig 1b), and performed an RNA fluorescence in situ hybridization (FISH) and immunofluorescence assay to examine the interaction between NEAT1, PSPC1, P54nrb, and SRSF2 in HSV-1 or Mock infected HeLa and C-33A cells

Summary

Introduction

Numbers of nuclear speckles and paraspeckles components have been demonstrated to regulate herpes simplex virus 1 (HSV-1) replication. Serine/arginine-rich splicing factor 2 (SRSF2), the core component of speckles, was associated with multiple paraspeckles components, including nuclear paraspeckles assembly transcript 1 (NEAT1), PSPC1, and P54nrb, in HSV-1 infected cells. This association coordinates the transcription of viral genes by binding to the promoters of these genes. Our previous studies demonstrated that components of the speckles, SRSF2, and components of the paraspeckles, NEAT1, P54nrb, and PSPC1, function to modulate HSV-1 replication and viral genes expression by binding these genes in order to alter their transcriptional activity[21,22]. NEAT1 and SRSF2 collaborate to regulate the histone modification of nearby viral genes through the association with enhancer of zeste homolog 2 (EZH2) and the P300/CBP complex

Methods

Results

Conclusion