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The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription.

ABSTRACT: The influenza A virus RNA polymerase is a heterotrimeric complex responsible for viral genome transcription and replication in the nucleus of infected cells. We recently carried out a proteomic analysis of purified polymerase expressed in human cells and identified a number of polymerase-associated cellular proteins. Here we characterise the role of one such host factors, SFPQ/PSF, during virus infection. Down-regulation of SFPQ/PSF by silencing with two independent siRNAs reduced the virus yield by 2-5 log in low-multiplicity infections, while the replication of unrelated viruses as VSV or Adenovirus was almost unaffected. As the SFPQ/PSF protein is frequently associated to NonO/p54, we tested the potential implication of the latter in influenza virus replication. However, down-regulation of NonO/p54 by silencing with two independent siRNAs did not affect virus yields. Down-regulation of SFPQ/PSF by siRNA silencing led to a reduction and delay of influenza virus gene expression. Immunofluorescence analyses showed a good correlation between SFPQ/PSF and NP levels in infected cells. Analysis of virus RNA accumulation in silenced cells showed that production of mRNA, cRNA and vRNA is reduced by more than 5-fold but splicing is not affected. Likewise, the accumulation of viral mRNA in cicloheximide-treated cells was reduced by 3-fold. In contrast, down-regulation of SFPQ/PSF in a recombinant virus replicon system indicated that, while the accumulation of viral mRNA is reduced by 5-fold, vRNA levels are slightly increased. In vitro transcription of recombinant RNPs generated in SFPQ/PSF-silenced cells indicated a 4-5-fold reduction in polyadenylation but no alteration in cap snatching. These results indicate that SFPQ/PSF is a host factor essential for influenza virus transcription that increases the efficiency of viral mRNA polyadenylation and open the possibility to develop new antivirals targeting the accumulation of primary transcripts, a very early step during infection.

SUBMITTER: Landeras-Bueno S

PROVIDER: S-EPMC3219729 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription.

Landeras-Bueno Sara S Jorba Núria N Pérez-Cidoncha Maite M Ortín Juan J

PLoS pathogens 20111117 11

The influenza A virus RNA polymerase is a heterotrimeric complex responsible for viral genome transcription and replication in the nucleus of infected cells. We recently carried out a proteomic analysis of purified polymerase expressed in human cells and identified a number of polymerase-associated cellular proteins. Here we characterise the role of one such host factors, SFPQ/PSF, during virus infection. Down-regulation of SFPQ/PSF by silencing with two independent siRNAs reduced the virus yiel ...[more]

PMID: 22114566

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Project description:Prostate cancer (PCa) patients commonly present with osteoblastic-type bone metastasis. Exosomes derived from tumor cells possess biological significance and can mediate intercellular communication in the tumor microenvironment. Long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) is also implicated in the stability in tumorigenesis and the development of PCa, but the underlying mechanism remains elusive. Hence, the current study set out to investigate the physiological mechanisms by which exosomes-encapsulated NEAT1 affects the progression of PCa. First, after isolation, we found PCa cell-derived exosomes induced the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). Besides, NEAT1 in PCa cells could be transferred into hBMSCs via exosomes. Further gain- and loss-of-function experimentation revealed that NEAT1 acted as a competing endogenous RNA (ceRNA) of microRNA (miR)-205-5p to upregulate the runt-related transcription factor 2 (RUNX2) levels. Moreover, NEAT1 could promote the RUNX2 expression via the splicing factor proline- and glutamine-rich (SFPQ)/polypyrimidine tract-binding protein 2 (PTBP2) axis. Functional assays uncovered that NEAT1 shuttled by PCa-exosomes facilitated the activity of alkaline phosphatase (ALP) and mineralization of extracellular matrix, and continuously upregulated the levels of RUNX2, ALP, alpha-1 type 1 collagen, and osteocalcin by regulating RUNX2, to induce the osteogenic differentiation of hBMSCs. Furthermore, in vivo experimentation confirmed that upregulated NEAT1 induced osteogenesis. Collectively, our findings indicated that PCa-derived exosomes-loaded NEAT1 upregulated RUNX2 to facilitate the osteogenesis of hBMSCs by competitively binding to miR-205-5p via the SFPQ/PTBP2 axis, therefore providing a potential therapeutic target to treat osteogenesis of hBMSCs in PCa. PCa cells secrete exosomes containing NEAT1, and NEAT1 exerts effects on osteogenic differentiation of hBMSCs in PCa. NEAT1 shuttled by PCa-derived exosomes could be transferred into hBMSCs, where NEAT1 exerted inductive properties in osteogenic differentiation of hBMSCs through the upregulation of RUNX2 by competitively binding to miR-205-5p and regulating SFPQ/PTBP2 in vitro and in vivo.

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The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription.

Publications

The splicing factor proline-glutamine rich (SFPQ/PSF) is involved in influenza virus transcription.

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