Transcriptome-wide identification of altered RNA m

Area of Science:

• Molecular Biology
• Cardiovascular Research
• Epigenetics

Background:

• Myocardial injury is a frequent complication of endotoxemia/sepsis, particularly in children, with poorly understood mechanisms and limited therapies.
• N6-methyladenosine (m6A) RNA modification is increasingly recognized for its role in physiological processes and disease, but its involvement in sepsis-induced myocardial injury is underexplored.

Purpose of the Study:

• To investigate the role of m6A modification in lipopolysaccharide (LPS)-induced myocardial injury.
• To construct an m6A modification map in a rat model of LPS-induced myocardial injury.

Main Methods:

• Established an adolescent rat model of myocardial injury via intraperitoneal lipopolysaccharide (LPS) injection.
• Quantified overall m6A modification levels and utilized MeRIP-seq and RNA-seq to identify differentially modified and expressed genes in cardiac tissue.
• Employed bioinformatics to analyze gene functions and qPCR to assess m6A-related enzyme expression.

Main Results:

• The overall level of m6A modification was significantly upregulated in the LPS-treated rat cardiac tissue compared to controls.
• Differentially m6A-modified and/or expressed genes were strongly associated with inflammatory responses and apoptosis pathways.
• Key m6A-related enzymes, including Mettl16, Rbm15, Fto, Ythdc2, and Hnrnpg, exhibited differential expression in response to LPS.

Conclusions:

• m6A modification is implicated in the pathogenesis of LPS-induced myocardial injury.
• The findings suggest that m6A modification influences myocardial injury by regulating inflammatory and apoptosis-related pathways.
• This study provides crucial insights into the molecular mechanisms underlying sepsis-induced myocardial injury.