导读：  余佳课题组在”Cell Research” 杂志发表研究论文“The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis（2017）”。研究中发现了一个RNA结合蛋白，QKI5能够在红系分化过程中激活primary miR-124-1（pri-124-1）的加工。QKI5识别一个远端QKI反应元件并通过与DGCR8的作用募集Microprocessor，随后通过两个互补序列的RNA-RNA相互作用将募集到的Microprocessor转移到pri-miR-124的茎环区。当红系分化时，QKI5表达下调，从而释放了与pri-miR-124结合的Microprocessor，导致成熟miR-124的数量减少。miR-124通过其靶基因TAL1和c-MYB调控红系的分化。更为重要的是，这种QKI5介导的调控会导致一个独特的miRNA表达谱，共同促进红系分化。链接：https://www.nature.com/cr/journal/v27/n3/full/cr201726a.html。

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        中国医学科学院基础医学研究所，“医学分子生物学国家重点实验室”的余佳研究团队通过研究发现RNA结合蛋白QKI5能够在红系分化过程中激活primary miR-124-1（pri-124-1）的加工。QKI5识别一个远端QKI反应元件并通过与DGCR8的作用募集Microprocessor，随后通过两个互补序列的RNA-RNA相互作用将募集到的Microprocessor转移到pri-miR-124的茎环区。当红系分化时，QKI5表达下调，从而释放了与pri-miR-124结合的Microprocessor，导致成熟miR-124的数量减少。miR-124通过其靶基因TAL1和c-MYB调控红系的分化。更为重要的是，这种QKI5介导的调控会导致一个独特的miRNA表达谱，共同促进红系分化。

       【摘要】： MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation. When erythropoiesis proceeds, the concomitant decrease of QKI5 releases Microprocessor from pri-124-1 and reduces mature miR-124 levels to facilitate erythrocyte maturation. Mechanistically, miR-124 targets TAL1 and c-MYB, two transcription factors involved in normal erythropoiesis. Importantly, this QKI5-mediated regulation also gives rise to a unique miRNA signature, which is required for erythroid differentiation. Taken together, these results demonstrate the pivotal role of QKI5 in primary miRNA processing during erythropoiesis and provide new insights into how a distal element on primary transcripts affects miRNA biogenesis.

     本文通讯作者为余佳研究员，第一作者为课题组王芳副教授。该研究工作得到了科技部国家重点研发计划基金的支持。

医学分子生物学国家重点实验室