全球miRNA剂量控制胚胎胚胎层的规格
Yingzi Cui1, Xuehui Lyu2, Li Ding1
1MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.
Nature
|May 6, 2021
概括
控制微RNA (miRNA) 剂量的新机制涉及DGCR8的替代转录启动,这对胚胎发育至关重要. 这一过程平衡了微处理器复合的功能,防止聚合,并确保干细胞命运的适当miRNA水平.
科学领域:
- 发育生物学
- 分子生物学
- 遗传学
背景情况:
- 微RNAs (miRNAs) 对胚胎发育和癌症至关重要,但控制它们的丰度的机制仍然不清楚.
- 微处理器复合体 (DROSHA和DGCR8) 对于miRNA生物生成至关重要.
- 在各种组织和瘤中观察到改变的miRNA水平,这凸显了精确的miRNA剂量控制的重要性.
研究的目的:
- 在胚胎发育过程中确定调节全球miRNA丰度的机制.
- 研究DGCR8调控对miRNA剂量的作用.
- 了解miRNA剂量如何影响干细胞分化和胚胎发育.
主要方法:
- 在小鼠胚胎干细胞中研究了DGCR8的替代转录启动 (ATI).
- 利用DGCR8mRNA的一个干环的遗传删除来研究它的影响.
- 分析了微处理器复合体立体测量,miRNA处理,成熟miRNA丰度和mRNA目标去抑制.
- 在体外和体内评估miRNA剂量调节失调对mES细胞多能性退出,脂质代谢和生殖层特异性的影响.
主要成果:
- 发现了一种由发育调节的miRNA剂量控制机制,涉及DGCR8的ATI.
- 删除DGCR8干循环导致DGCR8:DROSHA静态测量失衡,微处理器聚合,并减少了miRNA处理.
- 在胚胎发育过程中,miRNA剂量的调节失调改变了脂质代谢途径,并破坏了胚胎层的特异性.
- 已发现的miRNA剂量控制机制在人类中保持不变.
结论:
- 一个涉及DGCR8的促进器切换平衡了微处理器自动调节和聚合.
- 这种机制精确地控制全球miRNA剂量,对于决定干细胞命运至关重要.
- 这种miRNA剂量控制的失调会干扰胚胎发育,并与脂肪代谢的改变有关.
相关概念视频
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
01:22MicroRNAs
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...