RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells.
Nat Commun, 14(1):356.
Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitrythat coordinates gene expression at multiple levels from chromatin to mRNAprocessing. Recently, ribosome biogenesis and translation have emerged as keypathways that efficiently control stem cell homeostasis, yet the underlyingmolecular mechanisms remain largely unknown. Here, we identified RSL24D1 ashighly expressed in both mouse and human pluripotent stem cells. RSL24D1 isassociated with nuclear pre-ribosomes and is required for the biogenesis of 60Ssubunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairsglobal translation, particularly of key pluripotency factors and of componentsfrom the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact ondifferentiation, RSL24D1 depletion significantly alters ESC self-renewal andlineage commitment choices. Altogether, these results demonstrate thatRSL24D1-dependant ribosome biogenesis is both required to sustain the expressionof pluripotent transcriptional programs and to silence PRC2-regulateddevelopmental programs, which concertedly dictate ESC homeostasis.
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