【作者】 Fang Wang； Wei Song； Hongmei Zhao； Yuxia Li； Lei Dong； Yong Zhu； Mengmeng Zhang； Xiaoxia Ren； Shuailai Wu； Fei Miao； Wenjie Liu； Yanni Ma； Junwu Zhang； Aibin He； Jingyi Hui； Linfang Wang； 余佳；

【Author】 Fang Wang;Wei Song;Hongmei Zhao;Yuxia Li;Lei Dong;Yong Zhu;Mengmeng Zhang;Xiaoxia Ren;Shuailai Wu;Fei Miao;Wenjie Liu;Yanni Ma;Junwu Zhang;Aibin He;Jingyi Hui;Linfang Wang;Jia Yu;Department of Biochemistry,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC);

【机构】 Department of Biochemistry,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC)； 中国医学科学院基础研究所；

【摘要】 micro RNAs biogenesis has been finely controlled by complex layers of post-transcriptional regulations,including RNA-binding proteins(RBPs).Here we showed an RNA binding protein,QKI5,orchestrated the maturation of primary mi R-124-1(pri-124-1),transcriptionally activated by GATA-1,resulting in no accumulation of the final product mi R-124-1 during erythropoiesis.QKI5 associated with and recruited the micro RNAs processors DGCR8/Drosha to pri-124-1 for further processing at the early onset of ethryoid differentiation.However,at the late stage,the concomitant down-regulation of QKI5 released DGCR8/Drosha complex on pri-124-1 and reduced mature mi R-124-1 to facilitate the erythropoiesis.Further,gain of function of QKI5 restored pri-124-1 conversion in the cell-free extraction system.This QKI5-mediated regulation also gives rise to a unique mi RNA signature required for normal erythropoiesis.Together,we showed the pivotal role of QKI5 in DGCR8/Drosha-micro RNAs processing during erythropoiesis,providing an insight into functions of RBPs modulation of non-coding RNAs during normal development.更多还原

【Abstract】 micro RNAs biogenesis has been finely controlled by complex layers of post-transcriptional regulations,including RNA-binding proteins(RBPs).Here we showed an RNA binding protein,QKI5,orchestrated the maturation of primary mi R-124-1(pri-124-1),transcriptionally activated by GATA-1,resulting in no accumulation of the final product mi R-124-1 during erythropoiesis.QKI5 associated with and recruited the micro RNAs processors DGCR8/Drosha to pri-124-1 for further processing at the early onset of ethryoid differentiation.However,at the late stage,the concomitant down-regulation of QKI5 released DGCR8/Drosha complex on pri-124-1 and reduced mature mi R-124-1 to facilitate the erythropoiesis.Further,gain of function of QKI5 restored pri-124-1 conversion in the cell-free extraction system.This QKI5-mediated regulation also gives rise to a unique mi RNA signature required for normal erythropoiesis.Together,we showed the pivotal role of QKI5 in DGCR8/Drosha-micro RNAs processing during erythropoiesis,providing an insight into functions of RBPs modulation of non-coding RNAs during normal development.更多还原