Abstract:
The transcriptional regulation of skeletal muscle (SKM) development (myogenesis) has been documented for over 3 decades and served as a paradigm for tissue-specific cell type determination and differentiation. Myogenic stem cells (MuSC) in embryos and adult SKM are regulated by the transcription factors Pax3 and Pax7 for their stem cell characteristics, while their lineage determination and terminal differentiation are both dictated by the myogenic regulatory factors (MRF) that comprise Mrf4, Myf5, Myogenin, and MyoD. The myocyte enhancer factor Mef2c is activated by MRF during terminal differentiation and collaborates with them to promote myoblast fusion and differentiation. Recent studies have found critical regulation of these myogenic transcription factors at mRNA level, including subcellular localization, stability, and translational regulation. Therefore, the regulation of Pax3/7, MRFs and Mef2c mRNAs by RNA-binding factors and non-coding RNAs (ncRNA), including microRNAs and long non-coding RNAs (lncRNA), will be the focus of this review and the impact of this regulation on myogenesis will be further addressed. Interestingly, the stem cell characteristics of MuSC has been found to be critically regulated by ncRNAs, implying the involvement of ncRNAs in SKM homeostasis and regeneration. Current studies have further identified that some ncRNAs are implicated in the etiology of some SKM diseases and can serve as valuable tools/indicators for prediction of prognosis. The roles of ncRNAs in the MuSC biology and SKM disease etiology will also be discussed in this review.
摘要:
骨骼肌(SKM)发育(肌肉发生)的转录调节已被记录了30多年,并作为组织特异性细胞类型确定和分化的范例。胚胎和成体SKM中的成肌干细胞(MuSC)受转录因子Pax3和Pax7的调控,而它们的谱系确定和终末分化都是由包括Mrf4,Myf5,Myogenin,还有MyoD.肌细胞增强因子Mef2c在终末分化过程中被MRF激活,并与它们协作以促进成肌细胞融合和分化。最近的研究已经发现这些肌源性转录因子在mRNA水平的关键调控,包括亚细胞定位,稳定性,和翻译调节。因此,RNA结合因子和非编码RNA(ncRNA)对Pax3/7,MRFs和Mef2cmRNA的调节,包括microRNA和长链非编码RNA(lncRNA),这将是本次审查的重点,这一调控对肌生成的影响将进一步探讨。有趣的是,已发现MuSC的干细胞特征受到ncRNAs的关键调控,暗示ncRNAs参与SKM稳态和再生。目前的研究已经进一步确定,一些ncRNA与一些SKM疾病的病因学有关,并且可以用作预测预后的有价值的工具/指标。本文还将讨论ncRNAs在MuSC生物学和SKM疾病病因中的作用。