医学创新论坛第50期

CIMR Wednesday Lecture Series

时间：2024年12月4日（周三）下午16:00

地点：首都医科大学基础科研楼北楼一层逸夫报告厅

主持人：邓子厚

首都医学科学创新中心

报告人：程远明

南京大学现代生物研究院 研究员

报告题目：

RNA Epigenetic Regulation in Normal and Malignant Hematopoiesis

摘要：

N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA that is important for gene expression regulation. Here, a series of our studies indicated the essential role of m6A in normal and malignant hematopoiesis. Depletion of the m6A-forming enzyme METTL3 in human acute myeloid leukemia cells (AML) impairs cell proliferation and delays leukemia progression both in vitro and in vivo. Loss of METTL3 inhibits the translation of c-MYC, BCL2 and PTEN mRNAs and induces phosphorylated AKT, which contributes to the defects upon METTL3 depletion. Furthermore, we found that nuclear m6A reader YTHDC1 undergo liquid-liquid phase separation by binding to m6A RNA and form nuclear YTHDC1- m6A condensates (nYACs). nYACs enable YTHDC1 to protect m6A-mRNAs from exosome-associated RNA degradation and are required for AML cells to maintain cell survival and the undifferentiated state that is critical for leukemia maintenance. Overall, these results provide a rationale for the therapeutic targeting of m6A in myeloid leukemia. Moreover, by single cell RNA-seq, our results also indicate that RNA methylation controls symmetric commitment and cell identity of HSCs in normal hematopoiesis and provide a general mechanism for how stem cells regulate differentiation fate choice.

代表性论文：