Resumen de Cell-fate determination by ubiquitin-dependent regulation of translation
Achim Werner, Shintaro Iwasaki, Colleen A. McGourty, Sofia Medina Ruiz, Nia Teerikorpi, Indro Fedrigo, Nicholas T. Ingolia, Michael Rape
Metazoan development depends on the accurate execution of differentiation programs that allow pluripotent stem cells to adopt specific fates1. 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 (CUL3KBTBD8) as an essential regulator of human and Xenopus tropicalis neural crest specification. CUL3KBTBD8 monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome2,3. 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.
