造血红系分化是精密、复杂的调控体系，涉及多因子、多层次的协同作用，研究其调控规律、鉴定新的调节分子，具有重要的理论和实际意义。申请人基于前期工作，发现由于miRNA加工受阻而积聚的初级转录本，可能作为新型长非编码RNA（lnc-priRNA）调节红系分化。本项目将对红系分化过程中的lnc-priRNA进行系统性筛选和鉴定；在确认lnc-priRNA-182为研究对象后，分别在原代培养的造血干/祖细胞和小鼠移植模型中考察lnc-priRNA-182调节红系分化的生物学功能；并通过研究lnc-priRNA-182对染色质重塑蛋白SMARCA5的募集、进而对下游基因(包括红系分化、翻译相关基因)的转录激活、以及间接性对GATA-1 mRNA的翻译活化，阐明lnc-priRNA-182的详细分子机制。这不仅是红系分化过程中新型lncRNA、调控事件的全新揭示，更为丰富红系基因表达调控网络提供依据。

Normal erythropoiesis results in the generation of sufficient numbers of fully functional mature red blood cells. To achieve this goal, a number of regulatory factors which work at different layers, are necessary ingredients that used by erythroid precursor cells for effective erythropoiesis. In our previous studies, we have demonstrated that miRNA biogenesis is tightly regulated during erythropoiesis, especially when primary-miRNAs are processed into precursor-miRNAs. This regulation will lead to the accumulation of some un-processed primary-miRNAs, thus making the possibility that these primary-miRNAs may comprise a new type of long non-coding RNAs (refer to lnc-priRNA). In this study, we started from the screen and identification of candidate lnc-priRNA during erythropoiesis. As a result, we focused on the lnc-priRNA-182 to further analyze its regulatory roles during erythropoiesis in primary cultured hematopoietic stem/progenitor cells and mouse models of human hematopoietic stem cell transplantation. We further observed that lnc-priRNA-182 could recruit the chromatin remodeling protein SMARCA5, activate the transcription of both erythropoiesis and translation-associated genes, thus indirectly affecting GATA-1 mRNA translation. By clarifying the function and molecular mechanism of lnc-priRNA-182 in erythroid differentiation, it may provide new insights into this new lncRNA species, and provide new evidences of lncRNA study and the gene regulatory network in erythropoiesis.