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

Wang F¹, Song W¹, Zhao H¹, Ma Y¹, Li Y¹, Zhai D¹, Pi J¹, Si Y¹, Xu J¹, Dong L¹, Su R¹, Zhang M¹, Zhu Y¹, Ren X¹, Miao F¹, Liu W1, Li F¹, Zhang J¹, He A², Shan G³, Hui J⁴, Wang L¹, Yu J¹.

Cell Res. 2017 Mar;27(3):416-439. doi: 10.1038/cr.2017.26. Epub 2017 Feb 28.
PMID: 28244490，DOI: 10.1038/cr.2017.26

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.