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

Abstract

Background: Accelerated eosinophilic apoptosis is an important therapeutic strategy for bronchial asthma (BA).

Objective: To further reveal the molecular mechanism.

Methods: We selected RNA-seq data from cells in bronchoalveolar lavage fluid from patients with different severity levels. we performed principal component analysis (PCA) of the splicing ratios of differentially expressed genes (DEGs) between different samples. And we carried out overlapping analysis of DEGs in samples with known RBP genes. Then we analyzed the GO functions of the differentially expressed AS genes regulated by the differential expression of RBPs. We also analyzed the RBP-AS-GO network and analyzed RBPs and genes known to be involved in apoptosis and inflammation. Finally, we selected another set of data to verify the results.

Results: we identified nine highly expressed alternative splicing events, among which A3SS and A5SS had the highest incidence. The incidence of these alternative splicing events (ASEs) is closely related to the severity of BA. And we identified nine important RNA-binding proteins (RBPs). We obtained some AS genes were enriched in apoptosis- and inflammation-related pathways. Then we analyzed RBPs and genes known to be involved in apoptosis and inflammation. The results revealed that the expression levels of the selected RBPs were consistent in the two datasets and that the rate of AS events in both genes was increased.

Conclusion: We hypothesized that the regulation of AS by RBPs could affect apoptosis and inflammation in patients with severe asthma. We predicted that RBPs (PCBP4 and RPS29) and ASEs (A5SSs) are potential therapeutic targets for BA.