Li Yuxia, Bai Hua, Zhang Zhongzu, Li Weihua, Dong Lei, Wei Xueju, Ma Yanni, Zhang Junwu, Yu Jia, Sun Guotao, Wang Fang
Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), National Laboratory of Medical Molecular Biology, Beijing 100005, People's Republic of China ; Institute of Molecular Medicine, Medical School, Henan University, KaiFeng, 475000, People's Republic of China.
Mol Cells. 2014 Mar;37(3):213-9. doi: 10.14348/molcells.2014.2288. Epub 2014 Mar 6.
MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.
微小RNA（miRNA）是一类小的非编码调节RNA，在正常造血过程中发挥重要作用，包括红细胞生成。尽管研究已经鉴定出几种调节红系定向分化的miRNA，但我们并不清楚关键的红系转录因子GATA-1和NF-E2通过miRNA途径直接调节和控制分化的机制。在本研究中，我们鉴定出miR-199b-5p是人类红细胞生成的关键调节因子，其在K562细胞的红系分化过程中表达上调。此外，在红细胞成熟过程中，红系细胞中miR-199b-5p的增加以GATA-1和NF-E2依赖的方式发生。GATA-1和NF-E2均与miR-199b基因座上游结合并激活其转录。在K562细胞中强制表达miRNA-199b-5p会影响红系细胞的增殖和成熟。此外，我们鉴定出c-Kit是红系细胞中miR-199b-5p的直接靶标。综上所述，我们的结果在红系转录因子GATA-1/NF-E2、miR-199b-5p和c-Kit之间建立了功能联系，并为红系分化过程中转录和转录后调控的偶联提供了新的见解。
