The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2017,（3）
• 页码范围: 416-439
• 页数: 24页
• 语种: 英文
• DOI: 10.1038/cr.2017.26

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.