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氧化型和糖酵解型骨骼肌中 mA 甲基化修饰的长非编码 RNA 的综合分析

Comprehensive Analysis of Long Noncoding RNA Modified by mA Methylation in Oxidative and Glycolytic Skeletal Muscles.

机构信息

National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

出版信息

Int J Mol Sci. 2022 Apr 21;23(9):4600. doi: 10.3390/ijms23094600.

Abstract

N-methyladenosine (mA) is the most common modification in eukaryotic RNAs. Accumulating evidence shows mA methylation plays vital roles in various biological processes, including muscle and fat differentiation. However, there is a lack of research on lncRNAs' mA modification in regulating pig muscle-fiber-type conversion. In this study, we identified novel and differentially expressed lncRNAs in oxidative and glycolytic skeletal muscles through RNA-seq, and further reported the mA-methylation patterns of lncRNAs via MeRIP-seq. We found that most lncRNAs have one mA peak, and the mA peaks were preferentially enriched in the last exon of the lncRNAs. Interestingly, we found that lncRNAs' mA levels were positively correlated with their expression homeostasis and levels. Furthermore, we performed conjoint analysis of MeRIP-seq and RNA-seq data and obtained 305 differentially expressed and differentially mA-modified lncRNAs (dme-lncRNAs). Through QTL enrichment analysis of dme-lncRNAs and PPI analysis for their cis-genes, we finally identified seven key mA-modified lncRNAs that may play a potential role in muscle-fiber-type conversion. Notably, inhibition of one of the key lncRNAs, , delayed satellite cell differentiation and stimulated fast-to-slow muscle-fiber conversion. Our study comprehensively analyzed mA modifications on lncRNAs in oxidative and glycolytic skeletal muscles and provided new targets for the study of pig muscle-fiber-type conversion.

摘要

N6-甲基腺苷(m6A)是真核 RNA 中最常见的修饰。越来越多的证据表明,m6A 甲基化在包括肌肉和脂肪分化在内的各种生物学过程中发挥着重要作用。然而,lncRNAs 在调节猪肌肉纤维型转换中的 m6A 修饰研究还很缺乏。在这项研究中,我们通过 RNA-seq 鉴定了氧化型和糖酵解型骨骼肌中新型和差异表达的 lncRNAs,并通过 MeRIP-seq 进一步报告了 lncRNAs 的 m6A 修饰模式。我们发现大多数 lncRNAs 有一个 m6A 峰,m6A 峰优先富集在 lncRNAs 的最后一个外显子中。有趣的是,我们发现 lncRNAs 的 m6A 水平与其表达的稳定性和水平呈正相关。此外,我们对 MeRIP-seq 和 RNA-seq 数据进行了联合分析,获得了 305 个差异表达和差异 m6A 修饰的 lncRNAs(dme-lncRNAs)。通过对 dme-lncRNAs 的 QTL 富集分析和对其顺式基因的 PPI 分析,我们最终确定了七个可能在肌肉纤维型转换中发挥潜在作用的关键 m6A 修饰的 lncRNAs。值得注意的是,抑制其中一个关键的 lncRNA , ,延迟卫星细胞分化并刺激快肌向慢肌纤维转换。我们的研究全面分析了氧化型和糖酵解型骨骼肌中 lncRNAs 的 m6A 修饰,为猪肌肉纤维型转换的研究提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13e1/9105514/abe6fa9084f8/ijms-23-04600-g001.jpg

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