The miR-206/133b cluster is dispensable for development, survival and regeneration of skeletal muscle.
The miR-206/133b cluster is dispensable for development, survival and regeneration of skeletal muscle.
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DOI：
10.1186/s13395-014-0023-5
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发表时间：
2014
期刊：
影响因子：
4.9
通讯作者：
Braun T
中科院分区：
文献类型：
--
作者：
Boettger T;Wüst S;Nolte H;Braun T
三个不同的基因簇编码肌肉特异的miRNAs miR-206、miR-1和miR-133a/b，这两个miR-1/133a簇在心肌和骨骼肌中产生相同的成熟miR-1和miR-133a miRNAs，而同源的miR-206/133b簇仅在骨骼肌中表达。由于miRNAs miR-133a和miR-133b的序列几乎相同，因此它们似乎有可能共享潜在的靶标。同样，miR-1和miR-206在结构上相关，并包含对miRNA靶标识别重要的相同种子序列。过去，使用不同的体内和体外模型，这些miRNAs对骨骼肌的发育、功能和再生有不同的功能；然而，缺乏完整的miR-206/133b簇的突变体没有被分析，这些突变体产生一个单一的pri-miRNA组成一个功能单位。我们建立了miR-206/133b基因敲除小鼠，并对这些小鼠进行了形态分析；在转录组和蛋白质组水平上阐明了这个miRNA簇对体内骨骼肌发育、分化和再生的贡献；并进行了系统分析。此外，我们还研究了miR-206/133b基因缺失对Pax7表达和体外卫星细胞分化的影响。MiR-206/133b簇的缺失没有揭示miRNA簇对骨骼肌发育和分化的任何明显的必要功能。仔细检查miR-206/133b突变体的骨骼肌，发现在转录组和蛋白质组水平上没有结构变化或分子变化。与以前的研究相比，miR-206/133b簇的缺失不会损害MDX小鼠骨骼肌的再生。同样，miR-206/133b缺陷卫星细胞的体外分化没有受到影响，Pax7蛋白浓度也没有明显变化。我们的结论是miR-206/133b簇对于骨骼肌的发育、功能和再生是必不可少的，这可能是由于相关的miR-1/133a簇的功能重叠所致，这些簇在骨骼肌中强烈表达。我们推断，miR-206/133b簇本身并不是骨骼肌再生的基本调节因子，尽管可能存在在实验室条件下不明显的更微妙的功能。
Three different gene clusters code for the muscle-specific miRNAs miR-206, miR-1 and miR-133a/b. The two miR-1/133a clusters generate identical mature miR-1 and miR-133a miRNAs in heart and skeletal muscle, while the cognate miR-206/133b cluster is exclusively expressed in skeletal muscle. Since sequences of the miRNAs miR-133a and miR-133b are almost identical, it seems likely that they share potential targets. Similarly, miR-1 and miR-206 are structurally related and contain identical seed sequences important for miRNA-target recognition. In the past, different functions of these miRNAs were suggested for development, function and regeneration of skeletal muscle using different in vivo and in vitro models; however, mutants lacking the complete miR-206/133b cluster, which generates a single pri-miRNA constituting a functional unit, have not been analyzed. We generated miR-206/133b knock-out mice and analyzed these mice morphologically; at the transcriptome and proteome level to elucidate the contribution of this miRNA cluster for skeletal muscle development, differentiation, regeneration in vivo; and by systematic analysis. In addition, we studied the consequences of a genetic loss of miR-206/133b for expression of Pax7 and satellite cell differentiation in vitro. Deletion of the miR-206/133b cluster did not reveal any obvious essential function of the miRNA-cluster for development and differentiation of skeletal muscle. Careful examination of skeletal muscles of miR-206/133b mutants revealed no structural alterations or molecular changes at the transcriptome and proteome level. In contrast to previous studies, deletion of the miR-206/133b cluster did not impair regeneration of skeletal muscle in mdx mice. Likewise, differentiation of miR-206/133b deficient satellite cells in vitro was unaffected and no change in Pax7 protein concentration was apparent. We conclude that the miR-206/133b cluster is dispensable for development, function and regeneration of skeletal muscle, probably due to overlapping functions of the related miR-1/133a clusters, which are strongly expressed in skeletal muscle. We reason that the miR-206/133b cluster alone is not an essential regulator of skeletal muscle regeneration, although more subtle functions might exist that are not apparent under laboratory conditions.
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DOI：
10.1073/pnas.0602831103
发表时间：
2006-06-06
影响因子：
11.1
作者：
Rao, Prakash K.;Kumar, Roshan M.;Lodish, Harvey F.
通讯作者：
Lodish, Harvey F.
DOI：
10.1083/jcb.200603039
发表时间：
2006-10-09
期刊：
The Journal of cell biology
影响因子：
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作者：
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Tapscott SJ
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
DOI：
10.1083/jcb.200911036
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
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作者：
Chen JF;Tao Y;Li J;Deng Z;Yan Z;Xiao X;Wang DZ
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Wang DZ