RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells

Sébastien Durand, Marion Bruelle, Fleur Bourdelais, Bigitha Bennychen, Juliana Blin-Gonthier, Caroline Isaac, Aurélia Huyghe, Sylvie Martel, Antoine Seyve, Christophe Vanbelle, Annie Adrait, Yohann Couté, David Meyronet, Frédéric Catez, Jean-Jacques Diaz, Fabrice Lavial, Emiliano P. Ricci, François Ducray and Mathieu Gabut ()
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Sébastien Durand: Université Claude Bernard Lyon I, Centre Léon Bérard
Marion Bruelle: Université Claude Bernard Lyon I, Centre Léon Bérard
Fleur Bourdelais: Université Claude Bernard Lyon I, Centre Léon Bérard
Bigitha Bennychen: University of Ottawa
Juliana Blin-Gonthier: Laboratoire de Biologie et de Modélisation de la Cellule, ENS de Lyon, CNRS UMR 5239, Inserm U1293
Caroline Isaac: Université Claude Bernard Lyon I, Centre Léon Bérard
Aurélia Huyghe: Université Claude Bernard Lyon I, Centre Léon Bérard
Sylvie Martel: Université Claude Bernard Lyon I, Centre Léon Bérard
Antoine Seyve: Université Claude Bernard Lyon I, Centre Léon Bérard
Christophe Vanbelle: Université Claude Bernard Lyon I, Centre Léon Bérard
Annie Adrait: University Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, CEA, FR2048, 38000
Yohann Couté: University Grenoble Alpes, INSERM, CEA, UA13 BGE, CNRS, CEA, FR2048, 38000
David Meyronet: Université Claude Bernard Lyon I, Centre Léon Bérard
Frédéric Catez: Université Claude Bernard Lyon I, Centre Léon Bérard
Jean-Jacques Diaz: Université Claude Bernard Lyon I, Centre Léon Bérard
Fabrice Lavial: Université Claude Bernard Lyon I, Centre Léon Bérard
Emiliano P. Ricci: Laboratoire de Biologie et de Modélisation de la Cellule, ENS de Lyon, CNRS UMR 5239, Inserm U1293
François Ducray: Université Claude Bernard Lyon I, Centre Léon Bérard
Mathieu Gabut: Université Claude Bernard Lyon I, Centre Léon Bérard

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitry that coordinates gene expression at multiple levels from chromatin to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis, yet the underlying molecular mechanisms remain largely unknown. Here, we identified RSL24D1 as highly expressed in both mouse and human pluripotent stem cells. RSL24D1 is associated with nuclear pre-ribosomes and is required for the biogenesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors and of components from the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact on differentiation, RSL24D1 depletion significantly alters ESC self-renewal and lineage commitment choices. Altogether, these results demonstrate that RSL24D1-dependant ribosome biogenesis is both required to sustain the expression of pluripotent transcriptional programs and to silence PRC2-regulated developmental programs, which concertedly dictate ESC homeostasis.

Date: 2023
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DOI: 10.1038/s41467-023-36037-7

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