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

Front Endocrinol (Lausanne). 2023 Jul 21:14:1170957. doi: 10.3389/fendo.2023.1170957. eCollection 2023.

Abstract

Background: Polycystic ovary syndrome (PCOS) is a complex, multifactor disorder in women of reproductive age worldwide. Although RNA editing may contribute to a variety of diseases, its role in PCOS remains unclear.

Methods: A discovery RNA-Seq dataset was obtained from the NCBI Gene Expression Omnibus database of granulosa cells from women with PCOS and women without PCOS (controls). A validation RNA-Seq dataset downloaded from the European Nucleotide Archive Databank was used to validate differential editing. Transcriptome-wide investigation was conducted to analyze adenosine-to-inosine (A-to-I) RNA editing in PCOS and control samples.

Results: A total of 17,395 high-confidence A-to-I RNA editing sites were identified in 3,644 genes in all GC samples. As for differential RNA editing, there were 545 differential RNA editing (DRE) sites in 259 genes with Nucleoporin 43 (NUP43), Retinoblastoma Binding Protein 4 (RBBP4), and leckstrin homology-like domain family A member 1 (PHLDA) showing the most significant three 3'-untranslated region (3'UTR) editing. Furthermore, we identified 20 DRE sites that demonstrated a significant correlation between editing levels and gene expression levels. Notably, MIR193b-365a Host Gene (MIR193BHG) and Hook Microtubule Tethering Protein 3 (HOOK3) exhibited significant differential expression between PCOS and controls. Functional enrichment analysis showed that these 259 differentially edited genes were mainly related to apoptosis and necroptosis pathways. RNA binding protein (RBP) analysis revealed that RNA Binding Motif Protein 45 (RBM45) was predicted as the most frequent RBP binding with RNA editing sites. Additionally, we observed a correlation between editing levels of differential editing sites and the expression level of the RNA editing enzyme Adenosine Deaminase RNA Specific B1 (ADARB1). Moreover, the existence of 55 common differentially edited genes and nine differential editing sites were confirmed in the validation dataset.

Conclusion: Our current study highlighted the potential role of RNA editing in the pathophysiology of PCOS as an epigenetic process. These findings could provide valuable insights into the development of more targeted and effective treatment options for PCOS.

Keywords: A-to-I RNA editing; PCOS; apoptosis; cis-regulatory analysis; epigenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gene Expression Profiling
  • Granulosa Cells / metabolism
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Polycystic Ovary Syndrome* / genetics
  • Polycystic Ovary Syndrome* / metabolism
  • RNA Editing
  • RNA* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • RNA
  • RBM45 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins

Grants and funding

This project was supported by the National Natural Science Foundation of China (No. 31671311); the National First-Class Discipline Program of Light Industry Technology and Engineering (LITE2018-14); the “Six-Talent Peak” Plan of Jiangsu Province (No. SWYY-127); the Innovative and Entrepreneurial Talents of Jiangsu Province, the Program for High-Level Entrepreneurial and Innovative Talents of Jiangsu Province, Taihu Lake Talent Plan, and the Fundamental Research Funds for the Central Universities (JUSRP51712B and JUSRP1901XNC); the Postgraduate Research and Practice Innovation Program of Jiangsu Province (KYCX20_1946); the Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee (No. HB2020038); the Maternal and Child Health Research Project of Jiangsu in China (No. F202117); the Maternal and Child Health Research Project of Wuxi (No. FYKY201804); and the Excellent Program for Overseas Students of Wuxi in 2018 (No. 23).