Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
RNA Biol. 2021 Oct 15;18(sup1):439-450. doi: 10.1080/15476286.2021.1954380. Epub 2021 Jul 27.
RNA editing generates genetic diversity in mammals by altering amino acid sequences, miRNA targeting site sequences, influencing the stability of targeted RNAs, and causing changes in gene expression. However, the extent to which RNA editing affect gene expression via modifying miRNA binding site remains unexplored. Here, we first profiled the dynamic A-to-I RNA editome across tissues of Duroc and Luchuan pigs. The RNA editing events at the miRNA binding sites were generated. The biological function of the differentially edited gene in skeletal muscle was further characterized in pig muscle-derived satellite cells. RNA editome analysis revealed a total of 171,909 A-to-I RNA editing sites (RESs), and examination of its features showed that these A-to-I editing sites were mainly located in SINE retrotransposons PRE-1/Pre0_SS element. Analysis of differentially edited sites (DESs) revealed a total of 4,552 DESs across tissues between Duroc and Luchuan pigs, and functional category enrichment analysis of differentially edited gene (DEG) sets highlighted a significant association and enrichment of tissue-developmental pathways including TGF-beta, PI3K-Akt, AMPK, and Wnt signaling pathways. Moreover, we found that RNA editing events at the miRNA binding sites in the 3'-UTR of mRNA could prevent the miRNA-mediated mRNA downregulation of in the muscle-derived satellite (MDS) cell, consistent with the results obtained from the Luchuan skeletal muscle. This study represents the most systematic attempt to characterize the significance of RNA editing in regulating gene expression, particularly in skeletal muscle, constituting a new layer of regulation to understand the genetic mechanisms behind phenotype variance in animals. A-to-I: Adenosine-to-inosine; ADAR: Adenosine deaminase acting on RNA; RES: RNA editing site; DEG: Differentially edited gene; DES: Differentially edited site; FDR: False discovery rate; GO: Gene Ontology; KEGG: Kyoto Encyclopaedia of Genes and Genomes; MDS cell: musclederived satellite cell; RPKM: Reads per kilobase of exon model in a gene per million mapped reads; UTR: Untranslated coding regions.
RNA 编辑通过改变氨基酸序列、miRNA 靶序列、影响靶 RNA 的稳定性以及导致基因表达变化，在哺乳动物中产生遗传多样性。然而，通过修饰 miRNA 结合位点影响基因表达的 RNA 编辑程度仍未得到探索。在这里，我们首先对杜洛克和陆川猪不同组织中的动态 A-to-I RNA 编辑组进行了分析。鉴定出了 miRNA 结合位点的 RNA 编辑事件。进一步在猪肌肉卫星细胞中对骨骼肌中差异编辑基因的生物学功能进行了表征。RNA 编辑组分析共鉴定出 171909 个 A-to-I RNA 编辑位点（RES），对其特征的研究表明，这些 A-to-I 编辑位点主要位于 SINE 逆转座子 PRE-1/Pre0_SS 元件中。差异编辑位点（DES）分析显示，杜洛克和陆川猪之间的组织中共有 4552 个 DES，差异编辑基因（DEG）集的功能类别富集分析突出了组织发育途径的显著关联和富集，包括 TGF-β、PI3K-Akt、AMPK 和 Wnt 信号通路。此外，我们发现 3'UTR 中 mRNA 的 miRNA 结合位点的 RNA 编辑事件可以防止 miRNA 介导的 MDS 细胞中 mRNA 的下调，这与陆川骨骼肌的结果一致。本研究代表了对 RNA 编辑在调节基因表达中的意义进行特征描述的最系统尝试，特别是在骨骼肌中，构成了理解动物表型变异背后遗传机制的新调控层。A-to-I：腺苷到肌苷；ADAR：作用于 RNA 的腺苷脱氨酶；RES：RNA 编辑位点；DEG：差异编辑基因；DES：差异编辑位点；FDR：错误发现率；GO：基因本体论；KEGG：京都基因与基因组百科全书；MDS 细胞：肌肉卫星细胞；RPKM：每个基因百万映射读段中的外显子模型每千碱基的读段；UTR：非翻译编码区。
