title: The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis.
abstract: 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.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Wei
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authors.lastname: Song
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Hongmei
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authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Yanni
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authors.lastname: Ma
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Yuxia
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authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Jingnan
authors.initials: J
authors.lastname: Pi
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Yanmin
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authors.lastname: Si
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Jiayue
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authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Lei
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authors.lastname: Dong
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Rui
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authors.lastname: Su
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Mengmeng
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authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Junwu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Aibin
authors.initials: A
authors.lastname: He
authors.affiliation: School of Life Sciences, University of Sciences and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Shan
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Linfang
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authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100005, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D020014:K562 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D059372:Nucleotide Motifs / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D020598:Proto-Oncogene Proteins c-myb; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1 / Q000378:metabolism
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C000620563:RNA-binding protein QKI-5, human; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C067143:TAL1 protein, human; D012313:RNA