2. Academic Validation
  3. Cell-fate determination by ubiquitin-dependent regulation of translation

Cell-fate determination by ubiquitin-dependent regulation of translation

  • Nature. 2015 Sep 24;525(7570):523-7. doi: 10.1038/nature14978.
Achim Werner 1 2,  Shintaro Iwasaki 2,  Colleen A McGourty 2,  Sofia Medina-Ruiz 2,  Nia Teerikorpi 1 2,  Indro Fedrigo 2,  Nicholas T Ingolia 2,  Michael Rape 1 2
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
  • 2 Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
PMID: 26399832 DOI: 10.1038/nature14978
Abstract

Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates. Differentiation requires changes to chromatin architecture and transcriptional networks, yet whether other regulatory events support cell-fate determination is less well understood. Here we identify the ubiquitin ligase CUL3 in complex with its vertebrate-specific substrate adaptor KBTBD8 (CUL3(KBTBD8)) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome. Ubiquitylation drives formation of a TCOF1-NOLC1 platform that connects RNA polymerase I with ribosome modification enzymes and remodels the translational program of differentiating cells in favour of neural crest specification. We conclude that ubiquitin-dependent regulation of translation is an important feature of cell-fate determination.

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