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@ARTICLE{Rodschinka:281787,
      author       = {Rodschinka, Geraldine and Forcelloni, Sergio and Kühner,
                      Felix M and Wani, Sascha and Riemenschneider, Henrick and
                      Edbauer, Dieter and Behrens, Andrew and Nedialkova, Danny D},
      title        = {{C}omparative {CRISPR}i screens reveal a human stem cell
                      dependence on m{RNA} translation-coupled quality control.},
      journal      = {Nature structural $\&$ molecular biology},
      volume       = {32},
      number       = {10},
      issn         = {1545-9993},
      address      = {London [u.a.]},
      publisher    = {Nature Publishing Group},
      reportid     = {DZNE-2025-01180},
      pages        = {1932 - 1946},
      year         = {2025},
      abstract     = {The translation of mRNA into proteins in multicellular
                      organisms needs to be carefully tuned to changing proteome
                      demands in development and differentiation, while defects in
                      translation often have a disproportionate impact in distinct
                      cell types. Here we used inducible CRISPR interference
                      screens to compare the essentiality of genes with functions
                      in mRNA translation in human induced pluripotent stem cells
                      (hiPS cells) and hiPS cell-derived neural and cardiac cells.
                      We find that core components of the mRNA translation
                      machinery are broadly essential but the consequences of
                      perturbing translation-coupled quality control factors are
                      cell type dependent. Human stem cells critically depend on
                      pathways that detect and rescue slow or stalled ribosomes
                      and on the E3 ligase ZNF598 to resolve a distinct type of
                      ribosome collision at translation start sites on endogenous
                      mRNAs with highly efficient initiation. Our findings
                      underscore the importance of cell identity for deciphering
                      the molecular mechanisms of translational control in
                      metazoans.},
      keywords     = {Humans / RNA, Messenger: genetics / RNA, Messenger:
                      metabolism / Protein Biosynthesis / Induced Pluripotent Stem
                      Cells: metabolism / Induced Pluripotent Stem Cells: cytology
                      / CRISPR-Cas Systems / Ribosomes: metabolism / Cell
                      Differentiation / Myocytes, Cardiac: metabolism / Myocytes,
                      Cardiac: cytology / RNA, Messenger (NLM Chemicals)},
      cin          = {AG Edbauer},
      ddc          = {570},
      cid          = {I:(DE-2719)1110004},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40646310},
      pmc          = {pmc:PMC12527931},
      doi          = {10.1038/s41594-025-01616-3},
      url          = {https://pub.dzne.de/record/281787},
}