Hadj-Moussa Hanane, Moggridge Jason A, Luu Bryan E, Quintero-Galvis Julian F, Gaitán-Espitia Juan Diego, Nespolo Roberto F, Storey Kenneth B
Department of Biology and Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja, Valdivia, Chile.
Sci Rep. 2016 Apr 19;6:24627. doi: 10.1038/srep24627.
When faced with adverse environmental conditions, the marsupial Dromiciops gliroides uses either daily or seasonal torpor to support survival and is the only known hibernating mammal in South America. As the sole living representative of the ancient Order Microbiotheria, this species can provide crucial information about the evolutionary origins and biochemical mechanisms of hibernation. Hibernation is a complex energy-saving strategy that involves changes in gene expression that are elicited in part by microRNAs. To better elucidate the role of microRNAs in orchestrating hypometabolism, a modified stem-loop technique and quantitative PCR were used to characterize the relative expression levels of 85 microRNAs in liver and skeletal muscle of control and torpid D. gliroides. Thirty-nine microRNAs were differentially regulated during torpor; of these, 35 were downregulated in liver and 11 were differentially expressed in skeletal muscle. Bioinformatic analysis predicted that the downregulated liver microRNAs were associated with activation of MAPK, PI3K-Akt and mTOR pathways, suggesting their importance in facilitating marsupial torpor. In skeletal muscle, hibernation-responsive microRNAs were predicted to regulate focal adhesion, ErbB, and mTOR pathways, indicating a promotion of muscle maintenance mechanisms. These tissue-specific responses suggest that microRNAs regulate key molecular pathways that facilitate hibernation, thermoregulation, and prevention of muscle disuse atrophy.
当面临不利的环境条件时,有袋动物智利山鼩(Dromiciops gliroides)会利用每日或季节性的蛰伏来维持生存,它是南美洲已知的唯一一种会冬眠的哺乳动物。作为古老的微兽目(Microbiotheria)现存的唯一代表物种,该物种能够提供有关冬眠的进化起源和生化机制的关键信息。冬眠是一种复杂的节能策略,涉及部分由微小RNA引发的基因表达变化。为了更好地阐明微小RNA在调节低代谢中的作用,研究人员采用了改良的茎环技术和定量PCR来表征对照状态和处于蛰伏状态的智利山鼩肝脏和骨骼肌中85种微小RNA的相对表达水平。在蛰伏期间,有39种微小RNA受到差异调节;其中,35种在肝脏中表达下调,11种在骨骼肌中差异表达。生物信息学分析预测,肝脏中表达下调的微小RNA与丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶-蛋白激酶B(PI3K-Akt)和哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的激活有关,这表明它们在促进有袋动物蛰伏方面具有重要作用。在骨骼肌中,预测对冬眠有反应的微小RNA可调节粘着斑、表皮生长因子受体(ErbB)和mTOR信号通路,表明其对肌肉维持机制有促进作用。这些组织特异性反应表明,微小RNA调节着促进冬眠、体温调节和预防肌肉废用性萎缩的关键分子通路。