Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
Ye‐Chen Han, Hongzhi Xie, Bo Lu, Ruo‐Lan Xiang, Haipeng Zhang, Jingyi Li, Shuyang Zhang
Abstract
N6-methyladenosine (m 6 A) modification plays important roles in the pathology of a variety of diseases. However, the roles of m 6 A modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global m 6 A levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide m 6 A modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of m 6 A modifications during sepsis. Methylated lncRNAs and mRNAs were measured by m 6 A single-base site qPCR. The global m 6 A 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 m 6 A modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in m 6 A modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to m 6 A modifications in cardiac tissue during sepsis, and m 6 A modifications might be promising therapeutic targets.