Muscle-specific microRNA miR-206 promotes muscle differentiation.
Muscle-specific microRNA miR-206 promotes muscle differentiation.
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DOI：
10.1083/jcb.200603008
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发表时间：
2006-08-28
期刊：
影响因子：
--
通讯作者：
Dutta A
中科院分区：
文献类型：
--
作者：
Kim HK;Lee YS;Sivaprasad U;Malhotra A;Dutta A
三种肌肉特异性microRNA，miR-206，-1和-133，在体外C2 C12成肌细胞分化过程中被诱导。尽管存在血清，miR-206的转染仍促进分化，而通过反义寡核苷酸抑制microRNA抑制细胞周期撤回和分化，这通常由血清剥夺诱导。在许多被miR-206下调的mRNA中，DNA聚合酶α的p180亚基和其他三个基因被证明是直接靶点。聚合酶的下调抑制DNA合成，这是分化程序的重要组成部分。直接靶标通过依赖于预测的microRNA靶位点的mRNA切割而减少。然而，与小干扰RNA定向切割不同，切割片段的5′端是分布的，并且不限于靶位点，这表明外切核酸酶参与了降解过程。此外，肌原性转录因子Id 1 -3和MyoR的抑制剂在miR-206引入后减少，表明存在microRNA执行分化程序的其他机制。
Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase α and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA–directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.
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DOI：
10.1073/pnas.0403293101
发表时间：
2004-06-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
64.8
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30.8
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通讯作者：
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影响因子：
30.8
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影响因子：
64.8
作者：
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通讯作者：
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