基于多组学数据解析RNA A-to-I调控山羊肌细胞增殖分化的机制

解析肌肉生长发育的分子调控机制一直是肉用家畜遗传育种领域研究核心。作为一种广泛的转录后修饰，由ADAR催化产生的RNA A-to-I编辑通过改变RNA序列，多维度(mRNA-miRNA互作、蛋白重编码、可变剪切等)动态调控基因表达，是组织细胞发育特异性的重要驱动力。项目组前期利用山羊胚胎肌肉组织mRNA-seq数据已初步发现A-to-I编辑与肌肉发育密切相关。本研究拟以山羊骨骼肌卫星细胞(SMSCs)为主要材料，整合基因组、转录组(mRNA-、PacBio-、miRNA-seq)及4D-LFQ蛋白组数据，系统筛选SMSCs增殖分化中A-to-I调控的成肌基因及其介导的mRNA-miRNA互作、蛋白重编码和可变剪切，从而多层面解析A-to-I编辑调控山羊成肌分化的机制。本研究是阐明基因组、转录组和山羊肌肉发育之间复杂互作的重要步骤，对全面深入揭示动物肌肉生长发育的调控机制具有重大意义。

The molecular mechanism underpinning muscle development has always been the research spotlight in genetics and breeding of meat livestock. As a widespread post-transcriptional RNA modification, massive RNA A-to-I editing sites catalyzed by ADAR (Adenosine deaminase acting on RNA) dynamically regulates gene expression in multiple dimensions (via affecting mRNA-miRNA interaction, changing alternative splicing, and recoding protein) via altering RNA sequences, and it is a driven force for the specificity of animal tissue and cell development. Based on the mRNA-seq data from the muscle tissue of embryonic goat, we have preliminarily found that A-to-I editing is closely related to muscle development. In this study, using goat skeletal muscle satellite cells (SMSCs) as the main material, integrating multi-omics data including genome, transcriptome (mRNA-, miRNA-, and PacBio- sequencing) and proteome, we will systematically identify A-to-I editing sites in gene mRNA and miRNA during SMSCs proliferation and differentiation. Furthermore, we will anchor edited myogenic genes, and verify the effects of A-to-I on mRNA-miRNA interaction, protein recoding and alternative splicing, consequently illuminate the regulation mechanism of RNA A-to-I editing in myogenesis in multi-levels. Our study represents an important step toward elucidating the complex interactions between genome, transcriptome, and myogenesis, and will significantly supply basis for fully uncovering the regulation network of animal muscle growth and development.