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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Transcriptome sequencing analysis identified an alternative splicing regulatory network mediated by RNA-binding

Jingyi Zhang1, Mengqi Wang2, Dongxiao Yu1

  • 1Shandong University of Traditional Chinese Medicine, Jinan, China.

The Journal of Asthma : Official Journal of the Association for the Care of Asthma
|July 3, 2025
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Summary

Accelerated eosinophilic apoptosis is key for treating bronchial asthma (BA). This study reveals how RNA-binding proteins (RBPs) regulate alternative splicing (AS) events, impacting apoptosis and inflammation in severe BA, identifying potential therapeutic targets.

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genomics

Background:

  • Accelerated eosinophilic apoptosis is a crucial therapeutic strategy for bronchial asthma (BA).
  • Understanding the underlying molecular mechanisms is essential for developing effective treatments.
  • This study investigates the role of RNA-binding proteins (RBPs) and alternative splicing (AS) in BA pathogenesis.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which RBPs regulate AS in bronchial asthma.
  • To identify specific AS events and RBPs associated with BA severity.
  • To explore the link between RBP-mediated AS, apoptosis, and inflammation in severe BA.

Main Methods:

  • RNA sequencing (RNA-seq) data from bronchoalveolar lavage fluid of BA patients.
  • Principal Component Analysis (PCA) of splicing ratios for differentially expressed genes (DEGs).
  • Overlapping analysis of DEGs with known RBP genes, GO function analysis, and network construction.

Main Results:

  • Nine highly expressed alternative splicing events (ASEs) were identified, with A3SS and A5SS being most frequent and correlated with BA severity.
  • Nine key RBPs were identified, and their expression levels were consistent across datasets.
  • AS genes were enriched in apoptosis- and inflammation-related pathways, with increased AS event rates in severe BA.

Conclusions:

  • RBP-regulated AS influences apoptosis and inflammation in severe asthma.
  • RBPs (PCBP4, RPS29) and specific ASEs (A5SSs) are potential therapeutic targets for BA.
  • Further research into RBP-AS interactions may yield novel therapeutic strategies for bronchial asthma.