Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation

Publication date: 5 April 2018
Source:Cell Stem Cell, Volume 22, Issue 4
Author(s): Nina S. Corsini, Angela M. Peer, Paul Moeseneder, Mykola Roiuk, Thomas R. Burkard, Hans-Christian Theussl, Isabella Moll, Juergen A. Knoblich
Stem cell-specific transcriptional networks are well known to control pluripotency, but constitutive cellular processes such as mRNA splicing and protein synthesis can add complex layers of regulation with poorly understood effects on cell-fate decisions. Here, we show that the RNA binding protein HTATSF1 controls embryonic stem cell differentiation by regulating multiple aspects of RNA processing during ribosome biogenesis. HTATSF1, in a complex with splicing factor SF3B1, controls intron removal from ribosomal protein transcripts and regulates ribosomal RNA transcription and processing, thereby controlling 60S ribosomal abundance and protein synthesis. HTATSF1-dependent protein synthesis is essential for naive pre-implantation epiblast to transition into post-implantation epiblast, a stage with transiently low protein synthesis, and further differentiation toward neuroectoderm. Together, these results identify coordinated regulation of ribosomal RNA and protein synthesis by HTATSF1 and show that this essential mechanism controls protein synthesis during early mammalian embryogenesis.

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Teaser

Corsini et al. identify the splicing factor HTATSF1 as a regulator of intron retention specifically in ribosomal proteins and of ribosomal RNA transcription and processing to modulate levels of overall protein synthesis. They further demonstrate that HTATSF1-mediated protein synthesis dynamics control embryonic stem cell pluripotency and neuroectoderm differentiation.


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