Nucleolar protein PEXF controls ribosomal RNA synthesis and pluripotency exit

Area of Science:

• Cell Biology
• Molecular Biology
• Stem Cell Research

Background:

• Embryonic stem cells (ESCs) maintain pluripotency through coordinated protein synthesis and ribosome biogenesis (RiBi).
• ESCs exhibit low global protein synthesis and high RiBi levels.
• A transient reduction in RiBi is observed during the exit from pluripotency, but the regulatory mechanisms remain unclear.

Purpose of the Study:

• To identify the molecular mechanism regulating the transient reduction of ribosome biogenesis during the exit from pluripotency in human ESCs.
• To characterize the role of a novel nucleolar protein, pluripotency exit factor (PEXF), in this process.

Main Methods:

• Identification of PEXF as a protein encoded by the long noncoding RNA LINC00472.
• Investigation of PEXF's interaction with the rDNA promoter region.
• Analysis of PEXF's role in RNA polymerase I dissociation and pre-ribosomal RNA production using liquid-liquid phase separation principles.

Main Results:

• A previously uncharacterized nucleolar protein, PEXF, encoded by LINC00472, was identified.
• PEXF was found to dissociate RNA polymerase I from the rDNA promoter in a liquid-liquid phase separation-dependent manner.
• This dissociation inhibits pre-ribosomal RNA production, leading to a transient reduction in RiBi.

Conclusions:

• PEXF plays a crucial role in the transient reduction of ribosome biogenesis during the exit from pluripotency in human ESCs.
• The findings reveal a novel mechanism involving PEXF-mediated inhibition of RNA polymerase I activity.
• This study suggests that ribosome levels are a critical gatekeeper for exit from pluripotency in human ESCs.