Morin Pier, Dubuc Adrian, Storey Kenneth B
Institute of Biochemistry and Department of Chemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada.
Biochim Biophys Acta. 2008 Oct;1779(10):628-33. doi: 10.1016/j.bbagrm.2008.07.011. Epub 2008 Aug 5.
Mammalian hibernation includes long periods of profound torpor where the rates of all metabolic processes are strongly suppressed in a reversible manner. We hypothesized that microRNAs (miRNAs), small non-coding transcripts that bind to mRNA, could play a role in the global suppression of mRNA translation when animals enter torpor. Selected miRNA species (4-9 of the following: mir-1, mir-24, mir-15a, mir-16, mir-21, mir-122a, mir-143, mir-146 and mir-206) were evaluated in four organs of euthermic versus hibernating ground squirrels, Spermophilus tridecemlineatus using RT-PCR. Levels of mir-24 transcripts were significantly reduced in heart and skeletal muscle of torpid animals as were mir-122a levels in the muscle. Mir-1 and mir-21 both increased significantly in kidney during torpor by 2.0- and 1.3-fold, respectively. No changes were found for the four miRNA species analyzed in liver. Protein levels of Dicer, an enzyme involved in miRNA processing were also quantified in heart, kidney and liver. Dicer protein levels increased by 2.7-fold in heart during hibernation but decreased by 60% in kidney. These data are the first report that differential regulation of miRNA levels occurs during mammalian hibernation and they provide a mechanism for reversible gene silencing during torpor that can be rapidly reversed to allow renewed translation of mRNA when animals arouse back to euthermia.
哺乳动物的冬眠包括长时间的深度蛰伏,在此期间,所有代谢过程的速率都以可逆的方式受到强烈抑制。我们推测,微小RNA(miRNA),即与mRNA结合的小型非编码转录本,在动物进入蛰伏状态时可能在mRNA翻译的全局抑制中发挥作用。使用逆转录聚合酶链反应(RT-PCR)在正常体温的和正在冬眠的三线松鼠(Spermophilus tridecemlineatus)的四个器官中评估了选定的miRNA种类(以下4 - 9种:mir-1、mir-24、mir-15a、mir-16、mir-21、mir-122a、mir-143、mir-146和mir-·206)。蛰伏动物的心脏和骨骼肌中mir-24转录本水平显著降低,肌肉中的mir-122a水平也是如此。在蛰伏期间,肾脏中的Mir-1和mir-21分别显著增加了2.0倍和1.3倍。在所分析的四种miRNA种类中,肝脏未发现变化。还对参与miRNA加工的一种酶——Dicer的蛋白质水平在心脏、肾脏和肝脏中进行了定量。冬眠期间心脏中的Dicer蛋白质水平增加了2.7倍,但肾脏中降低了60%。这些数据是关于哺乳动物冬眠期间miRNA水平存在差异调节的首次报道,它们为蛰伏期间的可逆基因沉默提供了一种机制,当动物苏醒回到正常体温时,这种沉默可以迅速逆转,以使mRNA能够重新进行翻译。