a 2012

MicroRNAs regulate P21WAF1 / CIP 1 protein expression and the DNA damage response in human embryonic stem cells (hESCs)

DOLEŽALOVÁ, Dáša, Marek MRÁZ, Vladimír VINARSKÝ, Zuzana HOLUBCOVÁ, Josef JAROŠ et. al.

Basic information

Original name

MicroRNAs regulate P21WAF1 / CIP 1 protein expression and the DNA damage response in human embryonic stem cells (hESCs)

Authors

Edition

ISSCR 10th Annual Meeting, 13.-.16.6.2012, Yokohama, Japonsko, 2012

Other information

Language

English

Type of outcome

Konferenční abstrakt

Country of publisher

Japan

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

Tags

International impact
Změněno: 13/8/2012 11:38, Mgr. Martina Vráblíková

Abstract

V originále

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.