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

被引：600

作者：

Imamura, Katsutoshi ^{[1
]}

Imamachi, Naoto ^{[2
]}

Akizuki, Gen ^{[2
]}

Kumakura, Michiko ^{[3
,4
]}

Kawaguchi, Atsushi ^{[3
,4
]}

Nagata, Kyosuke ^{[3
,4
]}

Kato, Akihisa ^{[5
]}

Kawaguchi, Yasushi ^{[5
]}

Sato, Hiroki ^{[6
]}

Yoneda, Misako ^{[6
]}

Kai, Chieko ^{[6
]}

Yada, Tetsushi ^{[7
]}

Suzuki, Yutaka ^{[8
]}

Yamada, Toshimichi ^{[9
]}

Ozawa, Takeaki ^{[9
]}

Kaneki, Kiyomi ^{[10
]}

Inoue, Tsuyoshi ^{[10
]}

Kobayashi, Mika ^{[10
]}

Kodama, Tatsuhiko ^{[10
]}

Wada, Youichiro ^{[2
,10
]}

Sekimizu, Kazuhisa ^{[1
]}

Akimitsu, Nobuyoshi ^{[2
]}

机构：

[1] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1130033, Japan

[2] Univ Tokyo, Radioisotope Ctr, Tokyo 1130032, Japan

[3] Univ Tsukuba, Fac Med, Dept Infect Biol, Tsukuba, Ibaraki 3058575, Japan

[4] Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan

[5] Univ Tokyo, Inst Med Sci, Div Mol Virol, Dept Microbiol & Immunol, Tokyo 1088639, Japan

[6] Univ Tokyo, Inst Med Sci, Lab Anim Res Ctr, Tokyo 1088639, Japan

[7] Kyushu Inst Technol, Dept Biosci & Bioinformat, Fukuoka 8208502, Japan

[8] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol, Chiba 2778562, Japan

[9] Univ Tokyo, Sch Sci, Dept Chem, Tokyo 1130033, Japan

[10] Univ Tokyo, Res Ctr Adv Sci & Technol, Lab Syst Biol & Med, Tokyo 1538904, Japan

来源：

MOLECULAR CELL | 2014年 / 53卷 / 03期

基金：

日本学术振兴会;

关键词：

PATTERN-RECOGNITION RECEPTORS; GENE; BINDING; IDENTIFICATION; TRANSCRIPTION; CELLS; PSF; REPRESSOR; ELEMENTS; REVEALS;

D O I：

10.1016/j.molcel.2014.01.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：393 / 406

页数：14

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