Dynamic Patterns of N6-Methyladenosine Profiles of Messenger RNA Correlated with the Cardiomyocyte Regenerability during the Early Heart Development in Mice.
Dynamic Patterns of N6-Methyladenosine Profiles of Messenger RNA Correlated with the Cardiomyocyte Regenerability during the Early Heart Development in Mice.
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小鼠早期心脏发育过程中与心肌细胞再生能力相关的信使 RNA N6-甲基腺苷谱的动态模式
DOI：
10.1155/2021/5537804
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发表时间：
2021
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Yang Y;Shen S;Cai Y;Zeng K;Liu K;Li S;Zeng L;Chen L;Tang J;Hu Z;Xia Z;Zhang L
N6-甲基腺苷 (m6A) 在调节 mRNA 加工中发挥重要作用。尽管该领域取得了快速进展，但人们对 m6A 修饰在心肌发育和心肌细胞再生中的作用和机制知之甚少。现有研究表明，新生小鼠心脏组织具有增殖和再生能力，但其机制，特别是与m6A甲基化的关系尚不清楚。方法。为了系统地分析不同发育阶段小鼠心脏组织中 mRNA m6A 修饰模式，我们分别联合对 1 日龄、7 日龄和 28 日龄小鼠心脏组织进行甲基化 RNA 免疫沉淀测序（MeRIP-seq）和 RNA 测序（RNA-seq）。结果。我们确定了不同心脏发育阶段的 C57BL/6J 小鼠中差异表达的 mRNA 转录物与高甲基化或低甲基化 m6A 峰之间的联系和关联。结果显示，1日龄小鼠心脏中m6A峰数量和m6A修饰水平最低。相比之下，7 日龄小鼠的心脏组织往往拥有最多的 m6A 峰值和最高的总体 m6A 水平。然而，与1日龄相比，7日龄后心肌组织的m6A特征变化不大。具体来说，我们发现与 1 日龄小鼠心脏组织相比，7 日龄小鼠心脏组织中 1434 个甲基化基因中有 1269 个甲基化基因下调。一些特定基因的高甲基化可能与出生后第一天心脏强大的增殖和再生能力有关。就m6A密度而言，随着心脏发育的进展，趋势从编码序列（CDS）转移到3'非翻译区（3'UTR）和终止密码子。此外，一些基因在甲基化和表达方面表现出显着的变化，如kiss1、plekha6和megf6，它们可能在增殖中发挥重要作用。此外，与增殖高度相关的信号通路，如“Wnt信号通路”、“ECM-受体相互作用”和“心室形成”在1日龄甲基化基因中显着富集。结论。我们的结果揭示了不同的m6A修饰分布在不同发育阶段的C57BL/6J心脏组织中的模式，这为mRNA m6A甲基化在心肌发育和再生中的新功能提供了新的见解。
N6-Methyladenosine (m6A) plays important roles in regulating mRNA processing. Despite rapid progress in this field, little is known about the role and mechanism of m6A modification in myocardial development and cardiomyocyte regeneration. Existing studies have shown that the heart tissues of newborn mice have the capability of proliferation and regeneration, but its mechanism, particularly its relation to m6A methylation, remains unknown. Methods. To systematically profile the mRNA m6A modification pattern in the heart tissues of mice at different developmental stages, we jointly performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) of heart tissues of mice, respectively, aged 1 day old, 7 days old, and 28 days old. Results. We identified the linkages and association between differentially expressed mRNA transcripts and hyper or hypomethylated m6A peaks in C57BL/6J mice at different heart developmental stages. Results showed that the amount of m6A peaks and the level of m6A modification were the lowest in the heart of mice at 1 day old. By contrast, heart tissues from 7-day-old mice tended to possess the most m6A peaks and the highest global m6A level. However, the m6A characteristics of myocardial tissue changed little after 7 days old as compared to that of 1 day old. Specifically, we found 1269 downmethylated genes of 1434 methylated genes in 7-day-old mouse heart tissues as compared to those in 1-day-old mice. Hypermethylation of some specific genes may correlate with the heart's strong proliferative and regenerative capability at the first day after birth. In terms of m6A density, the tendency shifted from coding sequences (CDS) to 3′-untranslated regions (3′UTR) and stop codon with the progression of heart development. In addition, some genes demonstrated remarkable changes both in methylation and expression, like kiss1, plekha6, and megf6, which may play important roles in proliferation. Furthermore, signaling pathways highly related to proliferation such as “Wnt signaling pathway,” “ECM-receptor interaction,” and “cardiac chamber formation” were significantly enriched in 1-day-old methylated genes. Conclusions. Our results reveal a pattern that different m6A modifications are distributed in C57BL/6J heart tissue at different developmental stages, which provides new insights into a novel function of m6A methylation of mRNA in myocardial development and regeneration.
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影响因子：
38.3
作者：
Mahmoudi M;Yu M;Serpooshan V;Wu JC;Langer R;Lee RT;Karp JM;Farokhzad OC
通讯作者：
Farokhzad OC
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影响因子：
12.4
作者：
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通讯作者：
Cai B
影响因子：
3.7
作者：
Bodi Z;Bottley A;Archer N;May ST;Fray RG
通讯作者：
Fray RG
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影响因子：
37.8
作者：
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通讯作者：
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影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim