Transcriptome sequencing analysis identified an alternative splicing regulatory network mediated by RNA-binding...

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.