一个LINE1-Nucleolin的伙伴关系规范了早期发展和社会意识的认同
Michelle Percharde1, Chih-Jen Lin2, Yafei Yin3
1Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell
|June 26, 2018
概括
通常被视为垃圾DNA的LINE1逆转移素对早期发育至关重要. 它们调节关键基因和RNA合成,使胚胎干细胞自我更新和胚胎发育.
科学领域:
- 基因组学
- 发育生物学
- 分子生物学
背景情况:
- 包括LINE1逆转移体在内的可转移元素构成了哺乳动物基因组的重要组成部分.
- 矛盾的是,LINE1元素在早期发育过程中表达很高,尽管通常被认为是有害的.
- 它们在胚胎干细胞和早期胚胎形成中的确切功能在很大程度上仍未被探索.
研究的目的:
- 研究LINE1逆转移体在小鼠胚胎干细胞 (ESC) 和植入前胚胎中的重要作用.
- 阐明LINE1在早期发育过程中影响基因表达和细胞过程的分子机制.
主要方法:
- 分析LINE1RNA作为ESC中的核支架的作用.
- 调查LINE1RNA对Nucleolin和Kap1/Trim28的使用情况.
- 评估LINE1对Dux抑制和rDNA结合的影响.
- 评估LINE1对胚胎rRNA合成和发育进展的必要性.
主要成果:
- 在ESC中,LINE1RNA作为核支架,调用Nucleolin和Kap1/Trim28,抑制主调节器Dux.
- 这样可以促进rRNA合成和ESC自我更新.
- 在胚胎中,LINE1 RNA对于Dux沉默,rRNA合成和从2细胞阶段过渡至关重要.
结论:
- 在调节转录,发育效能和ESC自我更新方面,LINE1 RNA发挥着不可或缺的作用.
- 在关键的发育过程中,LINE1 RNA,Nucleolin,Kap1和周核染色体之间存在着重要的合作关系.
- 在哺乳动物的早期发育中,LINE1逆转移体不仅仅是垃圾DNA,而且是关键的功能元素.
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