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The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL.

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America January 21, 2014, Vol.111(3), pp.1002-1007
Main Author: Li, Zhonghan
Other Authors: Chao, Ti-Chun , Chang, Kung-Yen , Lin, Nianwei , Patil, Veena S , Shimizu, Chisato , Head, Steven R , Burns, Jane C , Rana, Tariq M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1313768111
Link: http://search.proquest.com/docview/1492678496/?pq-origsite=primo
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title: The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL.
format: Article
creator:
  • Li, Zhonghan
  • Chao, Ti-Chun
  • Chang, Kung-Yen
  • Lin, Nianwei
  • Patil, Veena S
  • Shimizu, Chisato
  • Head, Steven R
  • Burns, Jane C
  • Rana, Tariq M
subjects:
  • Cell Line–Metabolism
  • Cell Nucleolus–Metabolism
  • Cytokines–Metabolism
  • Enzyme-Linked Immunosorbent Assay–Metabolism
  • Gene Expression Profiling–Cytology
  • Gene Expression Regulation–Metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein L–Metabolism
  • Humans–Metabolism
  • Immunity, Innate–Metabolism
  • Inflammation–Metabolism
  • Interleukin-6–Metabolism
  • Macrophages–Metabolism
  • Mucocutaneous Lymph Node Syndrome–Metabolism
  • Oligonucleotide Array Sequence Analysis–Metabolism
  • RNA, Long Noncoding–Metabolism
  • Tumor Necrosis Factor-Alpha–Metabolism
  • Cytokines
  • Heterogeneous-Nuclear Ribonucleoprotein L
  • Interleukin-6
  • RNA, Long Noncoding
  • Tumor Necrosis Factor-Alpha
  • Toll-Like Receptors
  • Inflammation
  • Innate Immunity
ispartof: Proceedings of the National Academy of Sciences of the United States of America, January 21, 2014, Vol.111(3), pp.1002-1007
description: Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNF[alpha] expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNF[alpha] gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNF[alpha] expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNF[alpha] and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNF[alpha] expression and may play important roles in the innate immune response and inflammatory diseases in humans. innate immunity | inflammation | Toll-like receptors www.pnas.org/cgi/doi/10.1073/pnas.1313768111
language: eng
source:
identifier: E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1313768111
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleThe long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL.
creatorLi, Zhonghan ; Chao, Ti-Chun ; Chang, Kung-Yen ; Lin, Nianwei ; Patil, Veena S ; Shimizu, Chisato ; Head, Steven R ; Burns, Jane C ; Rana, Tariq M
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identifierE-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1313768111
subjectCell Line–Metabolism ; Cell Nucleolus–Metabolism ; Cytokines–Metabolism ; Enzyme-Linked Immunosorbent Assay–Metabolism ; Gene Expression Profiling–Cytology ; Gene Expression Regulation–Metabolism ; Heterogeneous-Nuclear Ribonucleoprotein L–Metabolism ; Humans–Metabolism ; Immunity, Innate–Metabolism ; Inflammation–Metabolism ; Interleukin-6–Metabolism ; Macrophages–Metabolism ; Mucocutaneous Lymph Node Syndrome–Metabolism ; Oligonucleotide Array Sequence Analysis–Metabolism ; RNA, Long Noncoding–Metabolism ; Tumor Necrosis Factor-Alpha–Metabolism ; Cytokines ; Heterogeneous-Nuclear Ribonucleoprotein L ; Interleukin-6 ; RNA, Long Noncoding ; Tumor Necrosis Factor-Alpha ; Toll-Like Receptors ; Inflammation ; Innate Immunity
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descriptionThousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNF[alpha] expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNF[alpha] gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNF[alpha] expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNF[alpha] and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNF[alpha] expression and may play important roles in the innate immune response and inflammatory diseases in humans. innate immunity | inflammation | Toll-like receptors www.pnas.org/cgi/doi/10.1073/pnas.1313768111
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