DND1通过招募CCR4-NOT复合体来维持生殖系干细胞的目标mRNA
Masashi Yamaji1, Miki Jishage2, Cindy Meyer1
1Howard Hughes Medical Institute and Laboratory for RNA Molecular Biology, The Rockefeller University, 1230 York Ave, Box 186, New York, New York 10065, USA.
Nature
|March 16, 2017
概括
在小鼠中,RNA结合蛋白DND1对于生殖细胞生存和瘤抑制至关重要. 它破坏特定的mRNA,调节细胞亡和干细胞多能性通路.
科学领域:
- 分子生物学
- 发育生物学
- 遗传学
背景情况:
- 结合RNA的蛋白DND1对于脊椎动物原始生殖细胞 (PGC) 的生存和预防生殖细胞瘤至关重要.
- 在调节基因表达和细胞命运方面,DND1的精确分子机制仍然不完全理解.
研究的目的:
- 阐明DND1控制目标mRNA稳定的分子机制.
- 确定DND1的直接点及其在PGC存活和干细胞维护中的作用.
主要方法:
- 通过RNA免疫沉,然后进行测序 (RIP-Seq) 来识别DND1结合点.
- 定量PCR和西式涂抹以验证目标mRNA的不稳定性.
- 转录组分析以评估DND1对基因表达特征的影响.
主要成果:
- DND1主要在目标mRNA的3' UTR中结合特定的UU(A/U) 三核酸基因.
- DND1 直接使用 CCR4-NOT 死亡酶复合体来破坏结合 mRNA 的稳定性.
- 在小鼠PGC和精子干细胞中,DND1介导的mRNA不稳定性至关重要.
- 目标RNA包括细胞亡,炎症和干细胞多能性通路的调节者 (例如,TGFβ超级家族).
结论:
- DND1通过破坏特定mRNA的稳定作用作为后转录抑制剂,从而调节细胞亡并维持干细胞多能性.
- DND1的功能对于生殖线发育和瘤抑制至关重要,可能是通过微调发育过渡.
- DND1与转录调节协同作用,以确保适当的生殖细胞发育和维持.
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