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

• Published in: Nature communications Vol. 14; no. 1; p. 356
• Main Authors: Durand, Sébastien, Bruelle, Marion, Bourdelais, Fleur, Bennychen, Bigitha, Blin-Gonthier, Juliana, Isaac, Caroline, Huyghe, Aurélia, Martel, Sylvie, Seyve, Antoine, Vanbelle, Christophe, Adrait, Annie, Couté, Yohann, Meyronet, David, Catez, Frédéric, Diaz, Jean-Jacques, Lavial, Fabrice, Ricci, Emiliano P., Ducray, François, Gabut, Mathieu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.01.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/19; 38/109; 38/39; 38/43; 38/89; 38/90; 38/91; 42/100; 45/70; 45/77; 631/136/2441; 631/136/2444; 631/337/100/2285; 631/337/574/1789; 631/532/2117; 82/29; 82/58; 82/80; 82/83; Animals; Biochemistry, Molecular Biology; Biosynthesis; Cell Differentiation - genetics; Cell self-renewal; Cellular Biology; Chromatin; Circuits; Depletion; Development Biology; Embryo cells; Embryology and Organogenesis; Embryonic Stem Cells - metabolism; Gene expression; Genomics; Homeostasis; Humanities and Social Sciences; Humans; Life Sciences; Mice; Molecular modelling; mRNA processing; multidisciplinary; Pluripotency; Pluripotent Stem Cells; Polycomb group proteins; Polycomb Repressive Complex 2 - metabolism; Ribosomes; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Subcellular Processes; Transcription factors; Translation; Yeast
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-36037-7

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. Pluripotency is coordinated at multiple levels of gene expression. Here the authors show that ribosome biogenesis is tightly regulated in embryonic stem cells (ESC) to control the translation of transcription and chromatin factors and dictate ESC fate.