RNA结合蛋白介导的miR-150作用机制的新发现及其在造血分化中的功能研究

造血分化发育是一个涉及多层次、多因子的复杂调控过程，然而对于其转录后层次的调控还较少有针对性研究，特别是对包括miRNA等非编码RNA、RNA结合蛋白，以及mRNA在内的众多转录后调控因子之间的相互作用更知之甚少。本课题以造血分化中起重要作用的RNA结合蛋白hnRNP E2为切入点，筛选和鉴定出了与其结合并发挥调节功能的miR-150，并在此基础上，分别在细胞系模型、原代培养的造血干细胞、及小鼠模型中研究miR-150如何协同hnRNP E2参与造血分化的调控。并结合hnRNP E2在白血病发生中的作用，进一步研究miR-150参与造血异常疾病的功能和分子机制。这不仅是对miRNA作用机制的全新解析，更为当前miRNA 的研究提供了新的思路，也为丰富和完善造血分化转录后调控网络提供依据。

Hematopoiesis is the process by which hematopoietic stem/progenitor cells (HPCs) give rise to lineage-committed precursors that terminally differentiate into mature circulating blood cells. It is modulated by highly orchestrated interactions of transcription factor, signaling pathway, and non-coding RNA. However, the intrinsic connection and cross-talk among the post-transcriptional modulators have not been well characterized in hematopoiesis. In this study, we screened the potential miRNAs that could directly bind to hnRNP E2, and identified miR-150 as a positive hit. Based on this, we will analyze the function of miR-150 in combination with hnRNP E2 during erythropoiesis in cell lines, primary cultured HPCs and mice. In addition, we will further study the involvement of miR-150 in leukemogenesis. It will provide new insights into miRNA study and the gene regulatory network in hematopoiesis.