Long Noncoding RNA NEAT1-Dependent SFPQ Relocation from Promoter Region to Paraspeckle Mediates IL8 Expression upon Immune Stimuli
Long Noncoding RNA NEAT1-Dependent SFPQ Relocation from Promoter Region to Paraspeckle Mediates IL8 Expression upon Immune Stimuli
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DOI：
10.1016/j.molcel.2014.01.009
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发表时间：
2014-02-06
期刊：
影响因子：
16
通讯作者：
Akimitsu, Nobuyoshi
中科院分区：
文献类型：
--
作者：
Imamura, Katsutoshi;Imamachi, Naoto;Akimitsu, Nobuyoshi
尽管细胞核中存在数千种长链非编码RNA（IncRNA），但只有几十种已被功能性表征。在这里，我们表明，核富集丰富的转录本1（NEAT 1），一个必不可少的IncRNA的形成核体paraspeckles，是诱导流感病毒和单纯疱疹病毒感染，以及Toll样受体3-p38通路触发的poly I：C刺激，导致paraspeckles的过度形成。我们发现NEAT 1促进抗病毒基因的表达，包括细胞因子如白细胞介素-8（IL-8）。我们发现，剪接因子脯氨酸/谷氨酰胺丰富（SFPQ），NEAT 1结合paraspeckle蛋白，是IL 8转录的阻遏物，和NEAT 1诱导重新定位SFPQ从IL 8启动子paraspeckles，导致IL 8的转录激活。总之，我们的数据表明，NEAT 1通过NEAT 1和SFPQ的刺激响应协同作用，通过抗病毒基因的转录调节，在先天免疫应答中起着重要作用。
Although thousands of long noncoding RNAs (IncRNAs) 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 IncRNA 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.