Department of Biomedical Sciences, Mercer University School of Medicine, Macon, Georgia.
Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California.
Am J Physiol Cell Physiol. 2020 May 1;318(5):C931-C942. doi: 10.1152/ajpcell.00166.2018. Epub 2020 Mar 4.
Alterations to muscle activity or loading state can induce changes in expression of myosin heavy chain (MHC). For example, sedentary individuals that initiate exercise training can induce a pronounced shift from IIx to IIa MHC. We sought to examine the regulatory response of MHC RNA in human subjects in response to exercise training. In particular, we examined how natural antisense RNA transcripts (NATs) are regulated throughout the MHC gene locus that includes MYH2 (IIa), MYH1 (IIx), MYH4 (IIb), and MYH8 (Neonatal) in vastus lateralis before and after a 5-wk training regime that consisted of a combination of aerobic and resistance types of exercise. The exercise program induced a IIx to IIa MHC shift that was associated with a corresponding increase in transcription on the antisense strand of the IIx MHC gene and a decrease in antisense transcription of the IIa MHC gene, suggesting an inhibitory mechanism mediated by NATs. We also report that the absence of expression of IIb MHC in human limb muscle is associated with the abundant expression of antisense transcript overlapping the IIb MHC coding gene, which is the opposite expression pattern as compared with that previously observed in rats. The NAT provides a possible regulatory mechanism for the suppressed expression of IIb MHC in humans. These data indicate that NATs may play a regulatory role with regard to the coordinated shifts in MHC gene expression that occur in human muscle in response to exercise training.
肌肉活动或负荷状态的改变可引起肌球蛋白重链（MHC）表达的变化。例如，开始运动训练的久坐个体可以从 IIx 向 IIa MHC 明显转变。我们试图检测运动训练对人类受试者 MHC RNA 的调节反应。特别是，我们检测了自然反义 RNA 转录物（NATs）在包括 MYH2（IIa）、MYH1（IIx）、MYH4（IIb）和 MYH8（新生儿）在内的 MHC 基因座中的调节情况，该基因座位于股外侧肌中，检测时间点分别为运动训练前和 5 周训练后，该训练方案由有氧运动和抗阻运动的组合组成。该运动方案诱导了 IIx 向 IIa MHC 的转变，这与 IIx MHC 基因反义链的转录相应增加以及 IIa MHC 基因反义转录减少有关，这表明 NATs 介导了一种抑制机制。我们还报告说，人类肢体肌肉中 IIb MHC 的缺失与重叠 IIb MHC 编码基因的反义转录本的大量表达有关，这与之前在大鼠中观察到的表达模式相反。NAT 为人类 IIb MHC 表达受抑制提供了一种可能的调节机制。这些数据表明，NATs 可能在运动训练引起的人类肌肉 MHC 基因表达的协调变化中发挥调节作用。
