Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue

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 le...

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Main Authors: Ye-Chen Han, Hong-Zhi Xie, Bo Lu, Ruo-Lan Xiang, Hai-Peng Zhang, Jing-Yi Li, Shu-Yang Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.670160/full
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author Ye-Chen Han
Hong-Zhi Xie
Bo Lu
Ruo-Lan Xiang
Hai-Peng Zhang
Jing-Yi Li
Shu-Yang Zhang
author_facet Ye-Chen Han
Hong-Zhi Xie
Bo Lu
Ruo-Lan Xiang
Hai-Peng Zhang
Jing-Yi Li
Shu-Yang Zhang
author_sort Ye-Chen Han
collection DOAJ
description 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.
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spelling doaj.art-e40dadb6fa3042d3ace7969fe07f6c202022-12-21T19:58:04ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-07-01810.3389/fmolb.2021.670160670160Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac TissueYe-Chen Han0Hong-Zhi Xie1Bo Lu2Ruo-Lan Xiang3Hai-Peng Zhang4Jing-Yi Li5Shu-Yang Zhang6Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing, ChinaPeking University Fifth School of Clinical Medicine (Beijing Hospital), Beijing, ChinaDepartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaN6-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.https://www.frontiersin.org/articles/10.3389/fmolb.2021.670160/fullN6-methyladenosinesepsismyocardial dysfunctionepitranscriptomicslncRNA
spellingShingle Ye-Chen Han
Hong-Zhi Xie
Bo Lu
Ruo-Lan Xiang
Hai-Peng Zhang
Jing-Yi Li
Shu-Yang Zhang
Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
Frontiers in Molecular Biosciences
N6-methyladenosine
sepsis
myocardial dysfunction
epitranscriptomics
lncRNA
title Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
title_full Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
title_fullStr Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
title_full_unstemmed Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
title_short Lipopolysaccharide Alters the m6A Epitranscriptomic Tagging of RNAs in Cardiac Tissue
title_sort lipopolysaccharide alters the m6a epitranscriptomic tagging of rnas in cardiac tissue
topic N6-methyladenosine
sepsis
myocardial dysfunction
epitranscriptomics
lncRNA
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.670160/full
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