3'UTR缩短缓解了对肌肉干细胞分化至关重要的mRNAs的miRNA抑制
Yi Zhu1, Jianshu Wang1, Deng Tong1
1Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.
The EMBO journal
|December 22, 2025
概括
替代性多基缩短肌肉干细胞分化过程中的3'未翻译区域,防止microRNA抑制并使再生成为可能. 这种3'未翻译区域的缩短对于肌肉的修复至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
背景情况:
- 替代多氨基化 (APA) 通过改变3'未翻译区域 (3UTR) 长度来调节基因表达.
- 通常,3UTR延长发生在细胞分化过程中.
研究的目的:
- 研究APA在肌肉干细胞 (卫星细胞,SC) 分化中的作用.
- 确定肌形成过程中APA的机制和功能意义.
主要方法:
- 在SC分化过程中分析了APA事件.
- 评估了3UTR缩短对微RNA (miRNA) 向的影响.
- 研究了在APA中裂变因子I (CFI) 的作用.
- 在试验室中,mRNA 3UTR的缩短受到干扰.
- 在体外研究了Matr3基因的APA-miRNA平衡.
- 检查了Matr3多基化位点突变对肌肉再生 in vivo的影响.
主要成果:
- 在SC分化过程中观察到偏好的APA介导的3UTR缩短,与预期相反.
- 发现肌肉特异性miRNAs (myomiRs) 的增加,向替代3UTRs.
- 证明减少CFI表达驱动3UTR缩短,使转录能够逃避myomiR抑制.
- 表明损害3UTR缩短阻碍了肌原分化.
- 突出了Matr3基因的APA-miRNA平衡在SC分化中的关键作用.
- 证实,突变Matr3的近端多化部位会在体内损害肌肉再生.
结论:
- 由APA介导的3UTR缩短在肌肉再生过程中对抗miRNA抑制.
- 这一过程对于编排强壮肌肉修复所需的基因表达程序至关重要.
- 这些发现揭示了一种对卫星细胞功能和肌肉平衡至关重要的新型调节机制.
相关概念视频
01:21Satellite Stem Cells and Muscular Dystrophy
2.3K
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
2.3K
01:13Formation of Muscle Fibers from Myoblasts
5.7K
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription...
5.7K
01:22MicroRNAs
3.7K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.7K
01:22MicroRNAs
23.8K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.8K
02:23Master Transcription Regulators
7.6K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K