Long Noncoding RNA NEAT1-Dependent SFPQ Relocation from Promoter Region to Paraspeckle Mediates IL8 Expression upon Immune Stimuli

Abstract

Although thousands of long noncoding RNAs (lncRNAs) are localized in the nucleus, only a few dozen have been functionally characterized. Here we show that nuclear enriched abundant transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, is induced by influenza virus and herpes simplex virus infection as well as by Toll-like receptor3-p38 pathway-triggered poly I:C stimulation, resulting in excess formation of paraspeckles. We found that NEAT1 facilitates the expression of antiviral genes including cytokines such as interleukin-8 (IL8). We found that splicing factor proline/glutamine-rich (SFPQ), a NEAT1-binding paraspeckle protein, is a repressor of IL8 transcription, and that NEAT1 induction relocates SFPQ from the IL8 promoter to the paraspeckles, leading to transcriptional activation of IL8. Together, our data show that NEAT1 plays an important role in the innate immune response through the transcriptional regulation of antiviral genes by the stimulus-responsive cooperative action of NEAT1 and SFPQ.

SWI/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies

“…Paraspeckles are ∼360 nm in diameter (8); hence, they are considered huge among RNP particles. Paraspeckles regulate the expression of a number of genes via the sequestration of specific proteins and RNAs (4,9,10), and are physiologically involved in the development of the corpus luteum and the mammary gland in mice (11,12).…”

Deep sequencing of the mouse lung transcriptome reveals distinct long non-coding RNAs expression associated with the high virulence of H5N1 avian influenza virus in mice

“…To date, several lncRNAs have been shown to play an important role in the innate immune response against influenza virus and be associated with viral pathogenesis, including NRAV (negative regulator of antiviral response)[11], NEAT1 (nuclear enriched abundant transcript 1)[30], Bst2/BISPR (bone marrow stromal cell antigen 2 IFN-stimulated positive regulator) [31,32] and VIN (virus inducible lincRNA)[33]. NRAV inhibits the transcription of interferon-stimulated genes via affecting histone modification of these genes (mainly MxA and IFITM3), resulting in the manipulation of the antiviral response[11].…”

“…In addition, the cooperative action between the transcriptional regulators and nuclear lncRNAs also impacts the innate immune response to IAV infection. NEAT1, an essential lncRNA for the formation of nuclear body paraspeckles, is activated by influenza virus and involved in the transcriptional activation of the antiviral gene interleukin Il8 probably through relocating transcriptional regulators splicing factor proline/glutamine-rich (SFPQ, a NEAT1-binding paraspeckle protein) from the I l8 promoter to the paraspeckles[30]. In addition, lncRNAs can also directly regulate the expression of specific protein-coding-genes.…”

“…As far as we known, only a few lncRNAs, such as NRAV (negative regulator of antiviral response)[11], NEAT1 (nuclear enriched abundant transcript 1)[30], Bst2/BISPR (bone marrow stromal cell antigen 2 IFN-stimulated positive regulator) [31,32] and VIN (virus inducible lincRNA) [33] have been demonstrated to be associated with the innate immunity against influenza virus and viral pathogenesis. Therefore, studies are still needed to better understand the potential roles of other lncRNAs in the pathogenesis of influenza virus.…”

Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA

“…Recently, two independent research groups reported that the NEAT1 -splicing factor proline and glutamine rich (SFPQ) interaction plays roles in both repression and activation of genes, which likely depend on the context of the promoter sequence or interplay with other transcriptional factors (43)(44) …”