Cellular quiescence uncouples the proteome from the transcriptome in neural stem cells

Area of Science:

• Cell Biology
• Molecular Biology
• Stem Cell Biology

Background:

• Quiescence is a vital cell-cycle arrest state protecting stem cells.
• Understanding quiescence regulation and markers remains incomplete.
• This state is crucial for development, tissue homeostasis, and cancer.

Purpose of the Study:

• To identify molecular mechanisms regulating quiescence.
• To uncover unique molecular markers for the quiescent state.
• To investigate post-transcriptional control of quiescence.

Main Methods:

• Utilized Drosophila and mammalian neural stem cells.
• Analyzed transcript localization (nuclear vs. cytoplasmic).
• Investigated transcript-nuclear speckle colocalization and SR-protein enrichment.

Main Results:

• Discovered selective nuclear enrichment of >2000 transcripts in quiescence.
• Observed nuclear transcript enrichment correlates with protein downregulation.
• Identified GA-rich multivalency and nuclear speckles in nuclear-biased transcripts.
• Evidence suggests regulated transcript processing for cell-cycle reentry.

Conclusions:

• Selective nuclear transcript enrichment is a key mechanism inhibiting translation in quiescence.
• This uncouples the transcriptome and proteome, a novel layer of post-transcriptional control.
• Findings provide new insights into quiescence regulation and potential therapeutic targets.