Programmed Double-stranded RNA Formation Enables Meiotic Stage Transitions

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Cell fate transitions require precise control of gene expression.
• Selective removal of pre-existing messenger RNAs (mRNAs) is crucial but poorly understood.
• Transcription factors orchestrate gene activation but their role in mRNA degradation is less clear.

Purpose of the Study:

• To investigate the mechanisms responsible for selective mRNA removal during cell fate transitions.
• To identify the role of double-stranded RNA (dsRNA) formation in this process.
• To understand how transcription factors regulate mRNA clearance.

Main Methods:

• Quantitative RNA structure analysis to detect dsRNA formation during meiosis.
• Long-read sequencing to identify and validate natural antisense transcripts (NATs).
• Analysis of transcription factor targets, including meiosis-specific factors like Ndt80p.

Main Results:

• Widespread dsRNA formation was observed during early-to-middle meiosis.
• Hundreds of NATs were identified, induced by meiosis-specific transcription factors.
• NATs paired with sense mRNAs, forming dsRNA aggregates targeted for vacuolar clearance via autophagy.
• This pathway selectively eliminated specific mRNAs, such as NDJ1, before metaphase I.

Conclusions:

• A novel pathway involving dsRNA formation and NATs mediates selective mRNA clearance during meiosis.
• Transcription factors play a dual role: activating stage-specific mRNAs and inducing NATs to remove preceding stage transcripts.
• This mechanism drives bidirectional transcriptome reprogramming for efficient cell fate transitions.