title: 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.
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Katsutoshi
authors: K
authors: Imamura
authors: Radioisotope Centre, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Naoto
authors: N
authors: Imamachi
authors: Radioisotope Centre, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Gen
authors: G
authors: Akizuki
authors: Department of Infection Biology, Faculty of Medicine & Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Michiko
authors: M
authors: Kumakura
authors: Department of Infection Biology, Faculty of Medicine & Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Atsushi
authors: A
authors: Kawaguchi
authors: Department of Infection Biology, Faculty of Medicine & Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors: Kyosuke
authors: K
authors: Nagata
authors: Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Akihisa
authors: A
authors: Kato
authors: Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Yasushi
authors: Y
authors: Kawaguchi
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Hiroki
authors: H
authors: Sato
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Misako
authors: M
authors: Yoneda
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors: Chieko
authors: C
authors: Kai
authors: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology Fukuoka 820-8502, Japan.
authors: Tetsushi
authors: T
authors: Yada
authors: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan.
authors: Yutaka
authors: Y
authors: Suzuki
authors: Department of Chemistry, School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Toshimichi
authors: T
authors: Yamada
authors: Department of Chemistry, School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Takeaki
authors: T
authors: Ozawa
authors: Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
authors: Kiyomi
authors: K
authors: Kaneki
authors: Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
authors: Tsuyoshi
authors: T
authors: Inoue
authors: Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
authors: Mika
authors: M
authors: Kobayashi
authors: Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
authors: Tatsuhiko
authors: T
authors: Kodama
authors: Radioisotope Centre, The University of Tokyo, Tokyo 113-0032, Japan; Laboratory for Systems Biology and Medicine, Research Centre for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan.
authors: Youichiro
authors: Y
authors: Wada
authors: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Kazuhisa
authors: K
authors: Sekimizu
authors: Radioisotope Centre, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: akimitsu@ric.u-tokyo.ac.jp.
authors: Nobuyoshi
authors: N
authors: Akimitsu
mesh_terms: D005786:Gene Expression Regulation; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D008459:Measles virus / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D000072670:PTB-Associated Splicing Factor; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; C577276:NEAT1 long non-coding RNA, human; D000072670:PTB-Associated Splicing Factor; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins