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@ARTICLE{Dormann:136697,
      author       = {Dormann, Dorothee and Madl, Tobias and Valori, Chiara F and
                      Bentmann, Eva and Tahirovic, Sabina and Abou-Ajram, Claudia
                      and Kremmer, Elisabeth and Ansorge, Olaf and Mackenzie, Ian
                      R A and Neumann, Manuela and Haass, Christian},
      title        = {{A}rginine methylation next to the {PY}-{NLS} modulates
                      {T}ransportin binding and nuclear import of {FUS}.},
      journal      = {The EMBO journal},
      volume       = {31},
      number       = {22},
      issn         = {0261-4189},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DZNE-2020-03019},
      pages        = {4258-4275},
      year         = {2012},
      abstract     = {Fused in sarcoma (FUS) is a nuclear protein that carries a
                      proline-tyrosine nuclear localization signal (PY-NLS) and is
                      imported into the nucleus via Transportin (TRN). Defects in
                      nuclear import of FUS have been implicated in
                      neurodegeneration, since mutations in the PY-NLS of FUS
                      cause amyotrophic lateral sclerosis (ALS). Moreover, FUS is
                      deposited in the cytosol in a subset of frontotemporal lobar
                      degeneration (FTLD) patients. Here, we show that arginine
                      methylation modulates nuclear import of FUS via a novel
                      TRN-binding epitope. Chemical or genetic inhibition of
                      arginine methylation restores TRN-mediated nuclear import of
                      ALS-associated FUS mutants. The unmethylated
                      arginine-glycine-glycine domain preceding the PY-NLS
                      interacts with TRN and arginine methylation in this domain
                      reduces TRN binding. Inclusions in ALS-FUS patients contain
                      methylated FUS, while inclusions in FTLD-FUS patients are
                      not methylated. Together with recent findings that FUS
                      co-aggregates with two related proteins of the FET family
                      and TRN in FTLD-FUS but not in ALS-FUS, our study provides
                      evidence that these two diseases may be initiated by
                      distinct pathomechanisms and implicates alterations in
                      arginine methylation in pathogenesis.},
      keywords     = {Active Transport, Cell Nucleus / Amino Acid Sequence /
                      Amyotrophic Lateral Sclerosis: genetics / Amyotrophic
                      Lateral Sclerosis: metabolism / Arginine: metabolism / Cell
                      Nucleus: metabolism / Frontotemporal Lobar Degeneration:
                      metabolism / Gene Silencing / HeLa Cells / Humans /
                      Karyopherins: genetics / Karyopherins: metabolism /
                      Methylation / Molecular Sequence Data / Nuclear Localization
                      Signals: metabolism / Proline: metabolism / Protein Binding
                      / Protein-Arginine N-Methyltransferases: genetics /
                      Protein-Arginine N-Methyltransferases: metabolism /
                      RNA-Binding Protein FUS: genetics / RNA-Binding Protein FUS:
                      metabolism / Repressor Proteins: genetics / Repressor
                      Proteins: metabolism / Signal Transduction / Tyrosine:
                      metabolism / Karyopherins (NLM Chemicals) / Nuclear
                      Localization Signals (NLM Chemicals) / RNA-Binding Protein
                      FUS (NLM Chemicals) / Repressor Proteins (NLM Chemicals) /
                      Tyrosine (NLM Chemicals) / Arginine (NLM Chemicals) /
                      Proline (NLM Chemicals) / PRMT1 protein, human (NLM
                      Chemicals) / Protein-Arginine N-Methyltransferases (NLM
                      Chemicals)},
      cin          = {AG Neumann},
      ddc          = {570},
      cid          = {I:(DE-2719)1210003},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22968170},
      pmc          = {pmc:PMC3501225},
      doi          = {10.1038/emboj.2012.261},
      url          = {https://pub.dzne.de/record/136697},
}