环状RNA CDR1as在山羊骨骼肌卫星细胞分化中的作用及分子海绵机制

肌肉生长的分子调控机制解析是肉羊分子育种改良的突破口。大量研究证实在肌细胞分化中，miRNA和lncRNA等非编码RNA的调控发挥了重要作用，但对于肌肉组织中广泛存在的环状非编码RNA（circRNA）在该过程中的作用及机制仍未见报道。申请人前期研究发现，环状RNA CDR1as与山羊骨骼肌卫星肌细胞（SMSCs）分化密切相关。本项目拟采用RNA-seq、Pulldown、FISH和RIP等技术筛选并验证CDR1as在SMSCs分化中的关键节点miRNAs，研究这些miRNAs的靶标mRNAs和lncRNAs富集的主要功能和代谢通路，全面解析CDR1as在SMSCs分化中的miRNAs分子海绵机制。本研究构建的CDR1as-miRNAs-mRNAs/lncRNAs肌细胞分化调控网络将代表肌肉组织表观遗传调控的又一个重要层次，对全面揭示肌肉生长发育的分子机制具有重要理论意义。

Uncovering the molecular regulation mechanism of muscle growth is considered as the breakthrough for meat-type goat breeding. Increasing evidence has shown that ncRNAs (noncoding RNAs), like miRNA (microRNA) and lncRNA (long noncoding RNA), play critical roles in regulating muscle cell differentiation. Nevertheless, as far as we known, there is no report on roles of circRNA (circular RNA), another type of ncRNA enriched in muscle, in the process and regulatory mechanism of muscle development. We have found out that circRNA CDR1as is closely related with differentiation of goat skeletal muscle satellite cells (SMSCs). Here, using RNA-seq, Pulldown, FISH and RIP, etc., we intend to screen and verify the critical miRNAs affected by CDR1as in differentiating SMSCs, and further study the main functions and metabolism pathways of these miRNA-targeted mRNAs and lncRNAs. Finally we will unveil the comprehensive ‘miRNAs molecular sponge’ mechanism of CDR1as in SMSCs. The CDR1as-miRNAs-mRNAs/lncRNAs networks constructed here will represent an important level of epigenetic regulation for muscle, and will have important theoretical significance for revealing the whole molecular mechanism of muscle growth and development as well.