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.

SUBMITTER: Han YC 

PROVIDER: S-EPMC8355517 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature