N6-Methyladenosine RNA Modification Regulates the Differential Muscle Development in Large White and Ningxiang Pigs.

IF 5.1 2区 生物学 Q2 CELL BIOLOGY Cells Pub Date : 2024-10-21 DOI:10.3390/cells13201744
Hao Gu, Kang Xu, Zhao Yu, Zufeng Ren, Fan Chen, Changfan Zhou, Wei Zeng, Hongyan Ren, Yulong Yin, Yanzhen Bi
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Abstract

N6-methyladenosine (m6A) is the most common modification in eukaryotic RNAs. Growing research indicates that m6A methylation is crucial for a multitude of biological processes. However, research on the m6A modifications in the regulation of porcine muscle growth is lacking. In this study, we identified differentially expressed genes in the neonatal period of muscle development between Large White (LW) and NingXiang (NX) pigs and further reported m6A methylation patterns via MeRIP-seq. We found that m6A modification regulates muscle cell development, myofibrils, cell cycle, and phosphatase regulator activity during the neonatal phase of muscle development. Interestingly, differentially expressed genes in LW and NX pigs were mainly enriched in pathways involved in protein synthesis. Furthermore, we performed a conjoint analysis of MeRIP-seq and RNA-seq data and identified 27 differentially expressed and m6A-modified genes. Notably, a typical muscle-specific envelope transmembrane protein, WFS1, was differentially regulated by m6A modifications in LW and NX pigs. We further revealed that the m6A modification accelerated the degradation of WFS1 in a YTHDF2-dependent manner. Noteworthy, we identified a single nucleotide polymorphism (C21551T) within the last exon of WFS1 that resulted in variable m6A methylation, contributing to the differing WFS1 expression levels observed in LW and NX pigs. Our study conducted a comprehensive analysis of the m6A modification on NX and LW pigs during the neonatal period of muscle development, and elucidated the mechanism by which m6A regulates the differential expression of WFS1 in the two breeds.

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N6-甲基腺苷RNA修饰调控大白猪和宁乡猪的肌肉发育差异
N6-甲基腺苷(m6A)是真核 RNA 中最常见的修饰。越来越多的研究表明,m6A 甲基化对多种生物过程至关重要。然而,有关 m6A 修饰在猪肌肉生长调控中的作用的研究还很缺乏。在这项研究中,我们鉴定了大白猪(LW)和宁乡猪(NX)新生儿期肌肉发育过程中的差异表达基因,并通过 MeRIP-seq 进一步报告了 m6A 甲基化模式。我们发现,在肌肉发育的新生阶段,m6A修饰调控着肌肉细胞发育、肌原纤维、细胞周期和磷酸酶调控因子的活性。有趣的是,LW 猪和 NX 猪的差异表达基因主要富集在参与蛋白质合成的通路中。此外,我们还对 MeRIP-seq 和 RNA-seq 数据进行了联合分析,发现了 27 个差异表达基因和 m6A 修饰基因。值得注意的是,一种典型的肌肉特异性包膜跨膜蛋白 WFS1 在 LW 猪和 NX 猪中受到 m6A 修饰的不同调控。我们进一步发现,m6A修饰以一种依赖于YTHDF2的方式加速了WFS1的降解。值得注意的是,我们在 WFS1 的最后一个外显子中发现了一个单核苷酸多态性(C21551T),该多态性导致了不同的 m6A 甲基化,从而导致了在 LW 猪和 NX 猪中观察到的不同的 WFS1 表达水平。我们的研究对 NX 猪和 LW 猪新生儿期肌肉发育过程中的 m6A 修饰进行了全面分析,并阐明了 m6A 调节两个品种 WFS1 不同表达的机制。
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来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
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