Identification of alternative splicing and RNA-binding proteins involved in myocardial ischemia-reperfusion injury

Abstract

Alternative splicing (AS) and RNA-binding proteins (RBPs) have been implicated in various cardiovascular diseases. Yet, a comprehensive understanding of their role in myocardial ischemia-reperfusion injury (MIRI) remains elusive. We aimed to identify potential therapeutic targets for MIRI by studying genome-wide changes in AS events and RBPs. We analyzed RNA-seq data from ischemia-reperfusion mouse models and the control group from the GSE130217 data set using Splicing Site Usage Variation Analysis software. We identified 28 regulated alternative splicing events (RASEs) and 47 differentially expressed RBP (DE-RBP) genes in MIRI. Most variable splicing events were involved in cassette exon, alternative 5' splice, alternative 3' splice, and retained intron types. Gene Ontology and Kyoto Encyclopedia of Genes (KOBAS 2.0 server) and Genomes pathway enrichment analyses showed that the differentially expressed variable splicing and RBP genes were mainly enriched in pathways related to myocardial function. The RBP-RASE network demonstrated a common variance relationship between DE-RBPs and RASEs, indicating that RBPs regulate variable shear events in MIRI. This study systematically identified important alterations in RASEs and RBPs in MIRI, expanding our understanding of the underlying pathogenesis of MIRI.

Keywords: RNA-binding proteins (RBPs); RNA-seq; myocardial ischemia–reperfusion injury (MIRI); regulated alternative splicing events (RASEs).