miR-378 and its host gene Ppargc1β exhibit independent expression in mouse skeletal muscle
miR-378 and its host gene Ppargc1β exhibit independent expression in mouse skeletal muscle
复制标题
DOI：
10.1093/abbs/gmaa061
复制
发表时间：
2020-08-01
影响因子：
3.7
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Kang, Lin;Han, Chunmiao;Zhang, Yong
microRNA（miRNAs）参与生理和病理环境中的多种生物学过程。近一半的已知miRNAs被归类为“内含子”miRNAs，因为它们嵌入蛋白质编码或非编码基因的内含子中。这种miRNAs被认为是从原始宿主基因转录物加工而来，并共享其宿主的启动子。最近的分析预测，一些内含子miRNAs可能作为独立的单位转录和调节，但在特定的生物学背景下，这一点几乎没有直接的证据。在这里，我们专注于miR-378，它位于过氧化物酶体增殖物激活受体的第一个内含子内。辅激活因子1-β（Ppargc 1 β）基因，并严格调节骨骼肌细胞分化和肌肉再生。我们证明了miR-378和Ppargc 1 beta在骨骼肌细胞分化过程中表现出不同的表达模式。在终末分化的成年小鼠骨骼肌组织中，miR-378主要在糖酵解肌中表达，而Ppargc 1 β主要在氧化比目鱼肌中表达。从机制上讲，miR-378而不是Ppargc 1 β在肌细胞中受转录因子MyoD的调节。我们的发现确定了miR-378表达的调控模型，从而帮助我们了解其在骨骼肌中的生理功能。
MicroRNAs (miRNAs) are implicated in multiple biological processes in physiological and pathological settings. Nearly half of the known miRNAs are classified as 'intronic' miRNAs because they are embedded within the introns of protein-coding or noncoding genes. Such miRNAs were thought to be processed from primary host gene transcripts and share the promoter of their host. Recent analyses predicted that some intronic miRNAs might be transcribed and regulated as independent units, but there is little direct evidence for this in a specific biological context. Here, we focused on miR-378, which is located within the first intron of the peroxisome proliferator-activated receptor. coactivator 1-beta (Ppargc1 beta) gene and critically regulates skeletal muscle cell differentiation and muscle regeneration. We demonstrate that miR-378 and Ppargc1 beta exhibit distinct expression patterns during skeletal muscle cell differentiation. In terminally differentiated adult skeletal muscle tissues of mice, miR-378 is predominantly expressed in glycolytic muscle, whereas Ppargc1 beta is mainly expressed in oxidative soleus muscle. Mechanistically, miR-378, but not Ppargc1 beta, is regulated by the transcription factor, MyoD, in muscle cells. Our findings identify a regulatory model of miR-378 expression, thereby helping us to understand its physiological function in skeletal muscle.