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@ARTICLE{Li:300827,
      author       = {T.-F. Li and P. Rothhaar and A. Lang and O. Grünvogel and
                      O. Colasanti and S. M. O. Ugarte and J. Traut and A. Piras
                      and N. Acosta-Rivero and V. Gonçalves Magalhães$^*$ and E.
                      Springer and A. Betz and H.-E. Huang and J. Park$^*$ and R.
                      Qiu and G. E. Gnouamozi and A.-K. Mehnert and V. L. D. Thi
                      and S. Urban and M. Muckenthaler and M. Schlesner$^*$ and D.
                      Wohlleber and M. Binder$^*$ and R. Bartenschlager$^*$ and A.
                      Pichlmair and V. Lohmann},
      title        = {{RBM}39 shapes innate immunity by controlling the
                      expression of key factors of the interferon response.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-00941},
      pages        = {1568056},
      year         = {2025},
      abstract     = {The contribution of innate immunity to clearance of viral
                      infections of the liver, in particular sensing via Toll-like
                      receptor 3 (TLR3), is incompletely understood. We aimed to
                      identify the factors contributing to the TLR3 response in
                      hepatocytes via CRISPR/Cas9 screening.A genome-wide
                      CRISPR/Cas9 screen on the TLR3 pathway was performed in two
                      liver-derived cell lines, followed by siRNA knockdown
                      validation. SiRNA knockdown and indisulam treatment were
                      used to study the role of RNA-binding motif protein 39
                      (RBM39) in innate immunity upon poly(I:C) or cytokine
                      treatment and viral infections. Transcriptome, proteome, and
                      alternative splicing were studied via RNA sequencing and
                      mass spectrometry upon depletion of RBM39.Our CRISPR/Cas9
                      screen identified RBM39, which is highly expressed in
                      hepatocytes, as an important regulator of the TLR3 pathway.
                      Knockdown of RBM39 or treatment with indisulam, an aryl
                      sulfonamide drug targeting RBM39 for proteasomal
                      degradation, strongly reduced the induction of
                      interferon-stimulated genes (ISGs) in response to
                      double-stranded RNA (dsRNA) or viral infections. RNA
                      sequencing (seq) and mass spectrometry identified that
                      transcription and/or splicing of the key pathway components
                      IRF3, RIG-I, and MDA5 were affected by RBM39 depletion,
                      along with multiple other cellular processes identified
                      previously. RBM39 knockdown further restrained type I and
                      type III IFN pathways by reducing the expression of
                      individual receptor subunits and STAT1/2. The function of
                      RBM39 was furthermore not restricted to hepatocytes.We
                      identified RBM39 as a regulatory factor of cell intrinsic
                      innate immune signaling. Depletion of RBM39 impaired TLR3,
                      RIG-I/MDA5, and IFN responses by affecting the basal
                      expression of key pathway components.},
      keywords     = {RNA-Binding Proteins: genetics / RNA-Binding Proteins:
                      metabolism / RNA-Binding Proteins: immunology / Immunity,
                      Innate: genetics / Humans / Toll-Like Receptor 3: metabolism
                      / Toll-Like Receptor 3: genetics / Toll-Like Receptor 3:
                      immunology / Hepatocytes: immunology / Hepatocytes:
                      metabolism / Signal Transduction / Interferons: immunology /
                      Interferons: metabolism / Gene Expression Regulation /
                      CRISPR-Cas Systems / Cell Line / IFNs (Other) / IRF3 (Other)
                      / RBM39 (Other) / STAT1 (Other) / STAT2 (Other) / splicing
                      (Other) / RNA-Binding Proteins (NLM Chemicals) / Toll-Like
                      Receptor 3 (NLM Chemicals) / Interferons (NLM Chemicals) /
                      TLR3 protein, human (NLM Chemicals)},
      cin          = {D430 / W610},
      ddc          = {610},
      cid          = {I:(DE-He78)D430-20160331 / I:(DE-He78)W610-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40330464},
      pmc          = {pmc:PMC12054253},
      doi          = {10.3389/fimmu.2025.1568056},
      url          = {https://inrepo02.dkfz.de/record/300827},
}