Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number...

Area of Science:

• Genetics
• Developmental Biology
• Molecular Biology

Background:

• Ribosomal DNA (rDNA) repeat maintenance is crucial for germline genome perpetuation.
• Drosophila melanogaster utilizes unequal sister chromatid exchange (USCE) for germline rDNA copy number (CN) expansion, initiated by DNA breaks.
• The rDNA-specific retrotransposon R2 mediates USCE but is typically repressed when rDNA CN is high to prevent DNA damage.

Approach:

• Identified the insulin receptor (InR) as a key regulator of R2 expression.
• Utilized single-cell RNA sequencing to analyze gene expression in male germline stem cells (GSCs).
• Investigated the impact of dietary manipulation on R2 expression and rDNA CN expansion.

Key Points:

• InR acts as a major repressor of R2 retrotransposon expression.
• Male GSCs exhibit reduced InR expression when rDNA CN is low, promoting R2 activity.
• Reduced InR signaling triggers R2 expression and subsequent rDNA CN expansion.
• Dietary interventions influence R2 expression and rDNA CN expansion.

Conclusions:

• The insulin pathway integrates rDNA CN status with environmental cues like diet.
• This mechanism provides a potential link between diet and heritable changes in genomic content.
• Understanding InR's role is vital for comprehending germline genome stability and adaptation.