Genes & Development · 2015 · 100 citations · 33 references
Life SciencesCell BiologyMolecular BiologyGene ExpressionRna ProcessingStem Cell BiologyEmbryonic Stem CellsRna InterferenceStem Cell ReprogrammingTranslation RegulationTranslational ControlTranslational RegulationGlobal Translational RegulationInduced Pluripotent Stem CellsMouse Embryonic Stem CellsPluripotencyPluripotency RegulationSmall Subunit ProcessomeStem Cell Fate DecisionsStem Cell Gene Regulation
RNA-binding proteins (RBPs) play integral roles in gene regulation, yet only a small fraction of RBPs has been studied in the context of stem cells. Here we applied an RNAi screen for RBPs in mouse embryonic stem cells (ESCs) and identified 16 RBPs involved in pluripotency maintenance. Interestingly, six identified RBPs, including Krr1 and Ddx47, are part of a complex called small subunit processome (SSUP) that mediates 18S rRNA biogenesis. The SSUP components are preferentially expressed in stem cells and enhance the global translational rate, which is critical to sustain the protein levels of labile pluripotency factors such as Nanog and Esrrb. Furthermore, the SSUP proteins are required for efficient reprogramming of induced pluripotent stem cells. Our study uncovers the role of the SSUP and the importance of translational control in stem cell fate decision.
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