Promoter-dependent nuclear RNA degradation ensures cell cycle-specific gene expression

Area of Science:

• Molecular Biology
• Cell Biology
• Gene Regulation

Background:

• Cell cycle progression relies on precise, phase-specific gene expression.
• Mechanisms controlling the timing and abundance of gene transcripts during the cell cycle are not fully understood.
• Nuclear RNA degradation's role in regulating gene expression timing requires further investigation.

Purpose of the Study:

• To investigate the role of nuclear RNA degradation in achieving cell cycle-dependent gene expression.
• To elucidate the mechanism by which RNA abundance is controlled during specific cell cycle phases.
• To determine the influence of promoter elements on RNA degradation and gene expression timing.

Main Methods:

• Utilized single-molecule quantification to measure RNA abundance across different cell cycle phases.
• Employed gene deletion strategies, specifically removing nuclear ribonucleases in Saccharomyces cerevisiae.
• Performed promoter replacement experiments to assess the impact on RNA degradation and cell cycle-specific expression.

Main Results:

• Demonstrated that nuclear RNA degradation machinery promotes cell cycle-dependent gene expression via promoter-dependent co-transcriptional RNA degradation.
• Showed that gene expression curtailment occurs even without complete transcriptional inhibition, highlighting the role of RNA degradation.
• Observed loss of phase-specific expression for the G1-specific gene AXL2 upon deletion of nuclear ribonucleases, with transcription detected throughout the cell cycle.
• Found that promoter replacement eliminated cell cycle-dependent RNA degradation and RNase sensitivity.

Conclusions:

• Nuclear RNA degradation is a key mechanism for regulating gene expression timing during the cell cycle.
• Promoter identity dictates the susceptibility of RNA to degradation, controlling transcript abundance.
• A novel model of gene regulation is proposed, where promoter-driven RNA degradation controls gene expression levels.