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@ARTICLE{Schott:128288,
      author       = {J. Schott$^*$ and S. Reitter$^*$ and J. Philipp$^*$ and K.
                      Haneke$^*$ and H. Schäfer and G. Stoecklin$^*$},
      title        = {{T}ranslational regulation of specific m{RNA}s controls
                      feedback inhibition and survival during macrophage
                      activation.},
      journal      = {PLoS Genetics},
      volume       = {10},
      number       = {6},
      issn         = {1553-7404},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {DKFZ-2017-04305},
      pages        = {e1004368 -},
      year         = {2014},
      abstract     = {For a rapid induction and efficient resolution of the
                      inflammatory response, gene expression in cells of the
                      immune system is tightly regulated at the transcriptional
                      and post-transcriptional level. The control of mRNA
                      translation has emerged as an important determinant of
                      protein levels, yet its role in macrophage activation is not
                      well understood. We systematically analyzed the contribution
                      of translational regulation to the early phase of the
                      macrophage response by polysome fractionation from mouse
                      macrophages stimulated with lipopolysaccharide (LPS).
                      Individual mRNAs whose translation is specifically regulated
                      during macrophage activation were identified by microarray
                      analysis. Stimulation with LPS for 1 h caused translational
                      activation of many feedback inhibitors of the inflammatory
                      response including NF-κB inhibitors (Nfkbid, Nfkbiz, Nr4a1,
                      Ier3), a p38 MAPK antagonist (Dusp1) and
                      post-transcriptional suppressors of cytokine expression
                      (Zfp36 and Zc3h12a). Our analysis showed that their
                      translation is repressed in resting and de-repressed in
                      activated macrophages. Quantification of mRNA levels at a
                      high temporal resolution by RNASeq allowed us to define
                      groups with different expression patterns. Thereby, we were
                      able to distinguish mRNAs whose translation is actively
                      regulated from mRNAs whose polysomal shifts are due to
                      changes in mRNA levels. Active up-regulation of translation
                      was associated with a higher content in AU-rich elements
                      (AREs). For one example, Ier3 mRNA, we show that repression
                      in resting cells as well as de-repression after stimulation
                      depends on the ARE. Bone-marrow derived macrophages from
                      Ier3 knockout mice showed reduced survival upon activation,
                      indicating that IER3 induction protects macrophages from
                      LPS-induced cell death. Taken together, our analysis reveals
                      that translational control during macrophage activation is
                      important for cellular survival as well as the expression of
                      anti-inflammatory feedback inhibitors that promote the
                      resolution of inflammation.},
      keywords     = {Adaptor Proteins, Signal Transducing (NLM Chemicals) /
                      Cytokines (NLM Chemicals) / IEX-1 protein, mouse (NLM
                      Chemicals) / Immediate-Early Proteins (NLM Chemicals) /
                      Lipopolysaccharides (NLM Chemicals) / NF-kappa B (NLM
                      Chemicals) / Nfkbiz protein, mouse (NLM Chemicals) / Nr4a1
                      protein, mouse (NLM Chemicals) / Nuclear Proteins (NLM
                      Chemicals) / Nuclear Receptor Subfamily 4, Group A, Member 1
                      (NLM Chemicals) / RNA, Messenger (NLM Chemicals) /
                      Tristetraprolin (NLM Chemicals) / Zfp36 protein, mouse (NLM
                      Chemicals) / p38 Mitogen-Activated Protein Kinases (NLM
                      Chemicals) / Ribonucleases (NLM Chemicals) / Zc3h12a
                      protein, mouse (NLM Chemicals) / Dual Specificity
                      Phosphatase 1 (NLM Chemicals) / Dusp1 protein, mouse (NLM
                      Chemicals)},
      cin          = {A200},
      ddc          = {570},
      cid          = {I:(DE-He78)A200-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24945926},
      pmc          = {pmc:PMC4063670},
      doi          = {10.1371/journal.pgen.1004368},
      url          = {https://inrepo02.dkfz.de/record/128288},
}