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RNA-binding proteins potentially regulate the alternative splicing of cell cycle-associated genes in proliferative

Ning Yang1, Ningzhi Zhang1, Guojing Lu1

  • 1Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China.

Scientific Reports
|March 21, 2024
PubMed

Insights

RNA-binding proteins (RBPs) drive proliferative diabetic retinopathy (PDR) by altering gene expression. This study identified key RBPs and their targets involved in cell cycle pathways, offering new therapeutic strategies for PDR.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Genetics

Background:

  • RNA-binding proteins (RBPs) are implicated in proliferative diabetic retinopathy (PDR) pathogenesis via alternative splicing events (ASEs).
  • The specific RBPs involved in PDR and their regulatory mechanisms remain largely uncharacterized.

Purpose of the Study:

  • To identify differentially expressed RBPs and alternative splicing genes (ASGs) in PDR neovascular membranes (NVM) and retinas.
  • To elucidate the RBP-AS regulatory network in PDR pathogenesis.

Main Methods:

  • Analysis of the public transcriptome dataset GSE102485 (PDR vs. normal retinas).
  • Screening for co-expression between top RBPs and ASGs.
  • Validation using an oxygen-induced retinopathy mouse model.

Main Results:

  • Identified 403 abnormally expressed RBPs in PDR NVM and retinal samples.
  • Functional analysis revealed enrichment of ASGs in cell cycle pathways.
  • Constructed an RBP-AS regulatory network comprising 15 RBPs and their target ASGs, with notable differential expression of SFPQ, MAP1B, HSP90AA1, MACF1, and CCNH in the mouse model.

Conclusions:

  • Established a novel RBP-AS interaction network crucial for PDR development.
  • Highlights the role of cell cycle-associated ASEs regulated by specific RBPs in PDR.
  • Provides insights for developing diagnostic and therapeutic strategies to prevent PDR-related blindness.

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