MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy

MicroRNA-1 and microRNA-133a expression are decreased during skeletal muscle hypertrophy
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DOI:
10.1152/japplphysiol.00932.2006
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发表时间:
2007-01-01
影响因子:
3.3
通讯作者:
Esser, Karyn A.
Esser, Karyn A.
中科院分区:
医学2区
文献类型:
--
作者:
McCarthy, John J.;Esser, Karyn A.

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MicroRNAs(MiRNAs)是一类高度保守的非编码RNA,参与转录后基因调控。少数肌肉特异的miRNAs已经被鉴定出来,并被证明在成肌细胞的增殖和分化以及胚胎肌肉的生长中起作用。本研究的主要目的是确定肌肉特异性miRNAs在比目鱼肌和足底肌中的表达水平,以及它们在足底肌中的表达是否因功能超负荷而改变。在所研究的miRNAs中,只有miRNA-206在比目鱼肌和足底肌间存在差异表达,初级miRNA(pri-miRNA)和成熟miRNA(MiR)在比目鱼肌中的表达都高出7倍。在7天的功能超负荷后,pri-miRNA-1-2和pri-miRNA-133a-2的转录水平都增加了近2倍,而pri-miRNA-206的转录水平增加了18.3倍。相反,miR-1和miR-133a的表达在超载后下调了约50%。超载后pri-miRNA和miR表达的差异不能用miRNA生物发生途径各组成部分表达的变化来解释,因为DROSHA和Exportin-5的转录水平在功能超载时显著增加了50%,而DICER的表达保持不变。这些结果首次报道了成年骨骼肌中肌肉特异性miRNAs表达的变化,并表明miRNAs可能在适应功能超负荷中发挥作用。
MicroRNAs ( miRNAs) are a class of highly conserved, noncoding RNAs involved in posttranscriptional gene regulation. A small number of muscle-specific miRNAs have been identified and shown to have a role in myoblast proliferation and differentiation as well as embryonic muscle growth. The primary objective of the present study was to determine the expression level of the muscle-specific miRNAs in the soleus and plantaris muscles and whether their expression in the plantaris was altered in response to functional overload. Of the miRNAs examined, only miRNA-206 was differentially expressed between soleus and plantaris muscles, as reflected by the sevenfold higher expression in the soleus for both the primary miRNA ( pri-miRNA) and mature miRNA ( miR). Following 7 days of functional overload, transcript levels for both pri-miRNA-1-2 and pri-miRNA-133a-2 increased by similar to 2-fold, whereas pri-miRNA-206 levels were elevated 18.3-fold. In contrast, expression of miR-1 and miR-133a were downregulated by similar to 50% following overload. The discrepancy between pri-miRNA and miR expression following overload was not explained by a change in the expression of components of the miRNA biogenesis pathway, since Drosha and Exportin-5 transcript levels were significantly increased by 50% in response to functional overload, whereas Dicer expression remained unchanged. These results are the first to report alterations in expression of muscle-specific miRNAs in adult skeletal muscle and suggest miRNAs may have a role in the adaptation to functional overload.