Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

Area of Science:

• Genomics
• Epigenetics
• Reproductive Medicine

Background:

• Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age.
• The role of RNA editing, specifically adenosine-to-inosine (A-to-I) editing, in PCOS pathogenesis is not well understood.

Purpose of the Study:

• To investigate the transcriptome-wide landscape of A-to-I RNA editing in granulosa cells from women with and without PCOS.
• To identify differentially edited genes and sites associated with PCOS and explore their functional implications.

Main Methods:

• Utilized RNA-Seq datasets from discovery and validation cohorts of PCOS and control granulosa cells.
• Performed transcriptome-wide analysis to identify A-to-I RNA editing sites and differential RNA editing (DRE) events.
• Conducted functional enrichment analysis and RNA binding protein (RBP) analysis.

Main Results:

• Identified 17,395 high-confidence A-to-I RNA editing sites in 3,644 genes.
• Discovered 545 DRE sites in 259 genes, with significant alterations in genes like NUP43, RBBP4, and PHLDA.
• Found correlations between editing levels and gene expression for 20 DRE sites, and confirmed 55 common differentially edited genes in the validation set.

Conclusions:

• RNA editing emerges as a potential epigenetic factor contributing to PCOS pathophysiology.
• Findings provide novel insights into PCOS mechanisms and may guide the development of targeted therapeutic strategies.