N6-methyladenosine (mA) modification plays important roles in the pathology of a variety of diseases. However, the roles of mA modification in sepsis-induced myocardial dysfunction are not well defined. Rats were divided into control and lipopolysaccharide (LPS)-induced sepsis group. Global mA levels of left ventricle tissue were measured by LC-MS/MS, and transcriptome-wide mA modifications were profiled using epitranscriptomic microarrays (mRNAs and lncRNAs). Bioinformatics analysis was conducted to understand the functional implications of mA modifications during sepsis. Methylated lncRNAs and mRNAs were measured by mA single-base site qPCR. The global mA 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 mA modification of Clec1b, Stk38l and Tnfrsf26 was associated with platelet activation and apoptotic pathways. Moreover, the decrease in mA modification of lncRNA XR_346,771 may be related to cation import in cardiac tissue. Our data provide novel information regarding changes to mA modifications in cardiac tissue during sepsis, and mA modifications might be promising therapeutic targets.
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| http://dx.doi.org/10.3389/fmolb.2021.670160 | DOI Listing |
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