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@ARTICLE{Hermann:300828,
      author       = {J. Hermann$^*$ and T. Bortecen$^*$ and R. Kalis and A.
                      Kowar$^*$ and C. Pechincha$^*$ and V. Vogt and M.
                      Schneider$^*$ and D. Helm$^*$ and J. Krijgsveld$^*$ and F.
                      Loayza-Puch$^*$ and J. Zuber and W. Palm$^*$},
      title        = {m{TORC}1 cooperates with t{RNA} wobble modification to
                      sustain the protein synthesis machinery.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00942},
      pages        = {4201},
      year         = {2025},
      note         = {DKFZ-ZMBH Alliance / #EA:A330#LA:A330#},
      abstract     = {Synthesizing the cellular proteome is a demanding process
                      that is regulated by numerous signaling pathways and RNA
                      modifications. How precisely these mechanisms control the
                      protein synthesis machinery to generate specific proteome
                      subsets remains unclear. Here, through genome-wide CRISPR
                      screens we identify genes that enable mammalian cells to
                      adapt to inactivation of the kinase mechanistic target of
                      rapamycin complex 1 (mTORC1), the central driver of protein
                      synthesis. When mTORC1 is inactive, enzymes that modify
                      tRNAs at wobble uridines (U34-enzymes), Elongator and
                      Ctu1/2, become critically essential for cell growth in vitro
                      and in tumors. By integrating quantitative nascent
                      proteomics, steady-state proteomics and ribosome profiling,
                      we demonstrate that the loss of U34-enzymes particularly
                      impairs the synthesis of ribosomal proteins. However, when
                      mTORC1 is active, this biosynthetic defect only mildly
                      affects steady-state protein abundance. By contrast,
                      simultaneous suppression of mTORC1 and U34-enzymes depletes
                      cells of ribosomal proteins, globally inhibiting
                      translation. Thus, mTORC1 cooperates with tRNA U34-enzymes
                      to sustain the protein synthesis machinery and support the
                      high translational requirements of cell growth.},
      keywords     = {Mechanistic Target of Rapamycin Complex 1: metabolism /
                      Mechanistic Target of Rapamycin Complex 1: genetics / RNA,
                      Transfer: metabolism / RNA, Transfer: genetics / Protein
                      Biosynthesis / Humans / Ribosomes: metabolism / Ribosomal
                      Proteins: metabolism / Ribosomal Proteins: genetics / HEK293
                      Cells / Animals / Proteomics / Uridine: metabolism /
                      Mechanistic Target of Rapamycin Complex 1 (NLM Chemicals) /
                      RNA, Transfer (NLM Chemicals) / Ribosomal Proteins (NLM
                      Chemicals) / Uridine (NLM Chemicals)},
      cin          = {A330 / B230 / B250 / W120},
      ddc          = {500},
      cid          = {I:(DE-He78)A330-20160331 / I:(DE-He78)B230-20160331 /
                      I:(DE-He78)B250-20160331 / I:(DE-He78)W120-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40328729},
      pmc          = {pmc:PMC12056009},
      doi          = {10.1038/s41467-025-59185-4},
      url          = {https://inrepo02.dkfz.de/record/300828},
}