Department of Life Sciences, National Central University, 300 Jhongda Rd, Jhongli, 32001, Taiwan.
J Muscle Res Cell Motil. 2024 Mar;45(1):21-39. doi: 10.1007/s10974-023-09663-3. Epub 2024 Jan 11.
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.
骨骼肌（SKM）发育（成肌分化）的转录调控已经被研究了超过 30 年，它为组织特异性细胞类型的确定和分化提供了范例。胚胎和成体 SKM 的成肌干细胞（MuSC）受转录因子 Pax3 和 Pax7 的调控，以保持其干细胞特性，而它们的谱系决定和终末分化则由肌调节因子（MRF）决定，这些因子包括 Mrf4、Myf5、Myogenin 和 MyoD。在终末分化过程中，肌细胞增强因子 Mef2c 被 MRF 激活，并与它们合作促进成肌细胞融合和分化。最近的研究发现，这些肌生成转录因子在 mRNA 水平上受到 RNA 结合因子和非编码 RNA（ncRNA）的调控，包括 microRNA 和长非编码 RNA（lncRNA）。因此，本文将重点讨论 Pax3/7、MRFs 和 Mef2c mRNA 被 RNA 结合因子和非编码 RNA（ncRNA），包括 microRNA 和长非编码 RNA（lncRNA）的调控，以及这种调控对成肌分化的影响。有趣的是，MuSC 的干细胞特性被发现受到 ncRNA 的严格调控，这表明 ncRNA 参与了 SKM 的稳态和再生。目前的研究还进一步确定，一些 ncRNA 与一些 SKM 疾病的病因有关，并且可以作为预测预后的有价值的工具/指标。本文还将讨论 ncRNA 在 MuSC 生物学和 SKM 疾病病因学中的作用。
