Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue

Abstract

N6-methyladenosine (m6A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m6A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m6A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m6A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m6A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m6A single-base site qPCR. The global m6A levels in left ventricle tissue were significantly decreased in the LPS group. While 27 transcripts (23 mRNAs and four lncRNAs) were hypermethylated, 46 transcripts (39 mRNAs and 7 lncRNAs) were hypomethylated in the LPS group. The mRNA expression of writers and readers was significantly decreased in the LPS group. The m6A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m6A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m6A modifications in cardiac tissue during sepsis, and m6A modifications might be promising therapeutic targets.

N6-methyladenosine (m6A) methyltransferase METTL3 regulates sepsis-induced myocardial injury through IGF2BP1/HDAC4 dependent manner

“…The emerging roles of m 6 A modification on sepsis-induced organ dysfunction have been gradually verified [ 26 – 28 ]. For example, in lipopolysaccharide (LPS)-induced endotoxemia on myocardial inflammation, the m 6 A-RNA methylation level and inflammatory cytokine genes increased, while FTO knockdown mimicked the effects [ 29 ].…”

Integrated Analysis of lncRNA and mRNA Expression Profiles Indicates Age-Related Changes in Meniscus

“… Shen et al (2021) found that decreased m 6 A levels of lncRNA-XR_343955 in rat aortic tissue affect the inflammatory response through the cell adhesion molecule pathway during lipopolysaccharide-induced sepsis. The decrease in m 6 A modification of lncRNA XR_346,771 may be related to cation import in rat cardiac tissue during sepsis ( Han et al, 2021 ). Moreover, the function of lncRNA is closely related to their subcellular localization.…”

m6A Methylation in Cardiovascular Diseases: From Mechanisms to Therapeutic Potential

“…m6A methylation pattern in cardiac tissue of septic shock rat model was found to be significantly different from control rat. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that differentially m6A-methylated mRNAs are mainly involved in interleukin-17 (IL17) signaling pathways, TNF signaling pathway, and cytokine receptor interaction pathway, suggesting that m6A methylation possibly participate in the progression of septic cardiomyopathy through immune and inflammatory response ( Han Y.-C. et al, 2021 ; Shen Z.-J. et al, 2021 ).…”