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.

Neoantigens in cancer immunotherapy: focusing on alternative splicing

“…Accurately identifying mRNA splicing events specific to tumors will be crucial for the effectiveness of immunotherapies targeting neoantigens ( 81 ). The advancement of RNA sequencing (RNA-seq) technologies provided available tools for screening AS events, However, the technique lacks the ability to detect splicing effects at the subclone level ( 82 , 83 ). Consequently, therapies targeting events present in only a fraction of the tumor may prove ineffective.…”

Functions of RNA-Binding Proteins in Cardiovascular Disease

“…In human hearts from ischemic HF patients, the RNA-binding proteins DDX52, RRS1, FCF1, DHX15, POLR1D, GNL2, RSL24D1, and EBNA1BP2 were found to be downregulated as compared to control hearts, while LSG1 and GRWD1 were upregulated in ischemic HF myocardium. Additionally, a recent study in mouse IRI myocardium demonstrated differential expression of RNAbinding proteins together with important alterations in splicing events of genes in pathways related to myocardial function [74].…”