生物
小RNA
胚胎干细胞
细胞生物学
下调和上调
DNA损伤
细胞周期
干细胞
基因表达调控
遗传学
DNA
基因
作者
Dáša Doležalová,Marek Mráz,Tomáš Bárta,Karla Plevová,Vladimír Vinarský,Zuzana Holubcová,Josef Jaroš,Petr Dvořák,Šárka Posp̂íšilová,Aleš Hampl
出处
期刊:Stem Cells
[Wiley]
日期:2012-06-18
卷期号:30 (7): 1362-1372
被引量:103
摘要
Abstract Studies of human embryonic stem cells (hESCs) commonly describe the nonfunctional p53-p21 axis of the G1/S checkpoint pathway with subsequent relevance for cell cycle regulation and the DNA damage response (DDR). Importantly, p21 mRNA is clearly present and upregulated after the DDR in hESCs, but p21 protein is not detectable. In this article, we provide evidence that expression of p21 protein is directly regulated by the microRNA (miRNA) pathway under standard culture conditions and after DNA damage. The DDR in hESCs leads to upregulation of tens of miRNAs, including hESC-specific miRNAs such as those of the miR-302 family, miR-371-372 family, or C19MC miRNA cluster. Most importantly, we show that the hESC-enriched miRNA family miR-302 (miR-302a, miR-302b, miR-302c, and miR-302d) directly contributes to regulation of p21 expression in hESCs and, thus, demonstrate a novel function for miR-302s in hESCS. The described mechanism elucidates the role of miRNAs in regulation of important molecular pathway governing the G1/S transition checkpoint before as well as after DNA damage.
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