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.
journal_name
Cell Resjournal_title
Cell researchauthors
Wang F,Song W,Zhao H,Ma Y,Li Y,Zhai D,Pi J,Si Y,Xu J,Dong L,Su R,Zhang M,Zhu Y,Ren X,Miao F,Liu W,Li F,Zhang J,He A,Shan G,Hui J,Wang L,Yu Jdoi
10.1038/cr.2017.26subject
Has Abstractpub_date
2017-03-01 00:00:00pages
416-439issue
3eissn
1001-0602issn
1748-7838pii
cr201726journal_volume
27pub_type
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