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Housekeeping Matters: How Splicing and Protein Synthesis Regulate Pluripotency and Development

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Review of “Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation” from Cell Stem Cell by Stuart P. Atkinson

We often consider housekeeping processes such as mRNA splicing and protein synthesis as constitutive cellular processes with no significant bearings on the mechanisms that control fate determination. However, a new study from the laboratory of Juergen A. Knoblich (Austrian Academy of Sciences, Vienna, Austria) now establishes that these underappreciated processes strongly influence cell fate during early mammalian development [1]. 

Specifically, Corsini et al. studied a role for the RNA binding protein HTATSF1 in human and mouse development given previous studies demonstrating how Drosophila HTATSF1/Barricade regulates stem cell lineages [2, 3], discovering the importance of the coordinated regulation of ribosomal RNA and protein synthesis to early mammalian embryogenesis.

The authors discovered that HTATSF1 interacted with the SF3B1 splicing factor (a component of the U2 snRNP complex) to regulate intron removal from ribosomal protein transcripts and with the PES1 and BOP1 large ribosomal subunit biogenesis factors to influence ribosomal RNA transcription and processing, thereby controlling 60S large ribosomal subunit abundance and regulating protein synthesis. 

The study then underlined the essential roles of HTATSF1-dependent protein synthesis control during early development: 1) mESCs in the naïve pluripotent state required HTATSF1 activity, 2) mESC differentiation and the transition of the naive pre-implantation epiblast to the post-implantation epiblast required a reduction in HTATSF1 activity, and finally 3) subsequent neuroectodermal differentiation required heightened HTATSF1 activity.

Overall, this new study reveals that constitutive cellular processes can strongly influence cell-fate transitions and early mammalian embryogenesis; we may not look at housekeeping in the same way again!

For more on the mechanisms that control pluripotency and embryo development, stay tuned to the Stem Cells Portal.

References

  1. Corsini NS, Peer AM, Moeseneder P, et al., Coordinated Control of mRNA and rRNA Processing Controls Embryonic Stem Cell Pluripotency and Differentiation. Cell Stem Cell 2018;22:543-558.e12.
  2. Neumüller Ralph A, Richter C, Fischer A, et al., Genome-Wide Analysis of Self-Renewal in <em>Drosophila</em> Neural Stem Cells by Transgenic RNAi. Cell Stem Cell 2011;8:580-593.
  3. Abramczuk MK, Burkard TR, Rolland V, et al., The splicing co-factor Barricade/Tat-SF1 is required for cell cycle and lineage progression in <em>Drosophila</em> neural stem cells. Development 2017;144:3932-3945.