XB-ART-51292
Nature
September 24, 2015;
525
(7570):
523-7.
Cell-fate determination by ubiquitin-dependent regulation of translation.
Werner A
,
Iwasaki S
,
McGourty CA
,
Medina-Ruiz S
,
Teerikorpi N
,
Fedrigo I
,
Ingolia NT
,
Rape M
.
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.
PubMed ID: 26399832
PMC ID: PMC4602398
Article link: Nature
Grant support: [+]
GM42341 NIGMS NIH HHS , R01 GM083064 NIGMS NIH HHS , S10RR025622 NCRR NIH HHS , S10RR027303 NCRR NIH HHS , R01 GM042341 NIGMS NIH HHS , HHMI_RAPE_M Howard Hughes Medical Institute , S10RR029668 NCRR NIH HHS , S10 RR029668 NCRR NIH HHS , S10 RR025622 NCRR NIH HHS , K99 DE025314 NIDCR NIH HHS, S10 RR027303 NCRR NIH HHS , Howard Hughes Medical Institute
Species referenced: Xenopus
Genes referenced: acta2 acta4 actc1 arrb1 arrb2 brd2 casp3.2 cul3 kbtbd8 nolc1 rpl28 smo tcof1 tp53
Morpholinos: cul3 MO1 kbtbd8 MO1 kbtbd8 MO2
Article Images: [+] show captions
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Anders, Differential expression analysis for sequence count data. 2011, Pubmed
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Barbieri, Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. 2012, Pubmed
Cambridge, Systems-wide proteomic analysis in mammalian cells reveals conserved, functional protein turnover. 2011, Pubmed
Chambers, Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. 2009, Pubmed
Dauwerse, Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. 2011, Pubmed
Dixon, Tcof1/Treacle is required for neural crest cell formation and proliferation deficiencies that cause craniofacial abnormalities. 2006, Pubmed
Freed, NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing. 2012, Pubmed
Gurdon, The egg and the nucleus: a battle for supremacy. 2013, Pubmed , Xenbase
Ingolia, The ribosome profiling strategy for monitoring translation in vivo by deep sequencing of ribosome-protected mRNA fragments. 2012, Pubmed
Jack, rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells. 2011, Pubmed
Jiang, Lack of Cul4b, an E3 ubiquitin ligase component, leads to embryonic lethality and abnormal placental development. 2012, Pubmed
Jin, Ubiquitin-dependent regulation of COPII coat size and function. 2012, Pubmed
Jin, Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. 2008, Pubmed , Xenbase
Jones, Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. 2008, Pubmed
Khokha, Techniques and probes for the study of Xenopus tropicalis development. 2002, Pubmed , Xenbase
Kondrashov, Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. 2011, Pubmed
Lander, The F-box protein Ppa is a common regulator of core EMT factors Twist, Snail, Slug, and Sip1. 2011, Pubmed , Xenbase
Louis-Dit-Picard, KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. 2012, Pubmed
McCann, Genetics. Mysterious ribosomopathies. 2013, Pubmed
Petroski, Function and regulation of cullin-RING ubiquitin ligases. 2005, Pubmed
Price, Analysis of proteome dynamics in the mouse brain. 2010, Pubmed
Rape, The processivity of multiubiquitination by the APC determines the order of substrate degradation. 2006, Pubmed
Silverman, SCF ubiquitin ligases in the maintenance of genome stability. 2012, Pubmed
Singer, Cullin-3 targets cyclin E for ubiquitination and controls S phase in mammalian cells. 1999, Pubmed
Skaar, Mechanisms and function of substrate recruitment by F-box proteins. 2013, Pubmed
Sondalle, Human diseases of the SSU processome. 2014, Pubmed
Sowa, Defining the human deubiquitinating enzyme interaction landscape. 2009, Pubmed
Tuck, A transcriptome-wide atlas of RNP composition reveals diverse classes of mRNAs and lncRNAs. 2013, Pubmed
Voigt, A dominant-negative form of the E3 ubiquitin ligase Cullin-1 disrupts the correct allocation of cell fate in the neural crest lineage. 2006, Pubmed , Xenbase
Wang, Deletion of the Cul1 gene in mice causes arrest in early embryogenesis and accumulation of cyclin E. 1999, Pubmed
Welcker, FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. 2008, Pubmed
Xue, Specialized ribosomes: a new frontier in gene regulation and organismal biology. 2012, Pubmed
Yanai, Mapping gene expression in two Xenopus species: evolutionary constraints and developmental flexibility. 2011, Pubmed , Xenbase
Yoon, Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. 2006, Pubmed
Zlotorynski, Development: Ubiquitylation determines cell fate. 2015, Pubmed