SRSF3 recruits DROSHA to the basal junction of primary microRNAs
- 1Center for RNA Research, Institute for Basic Science, Seoul 08826, Korea
- 2School of Biological Sciences, Seoul National University, Seoul 08826, Korea
- 3Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China
- 4HKUST Shenzhen Research Institute, Shenzhen 518057, China
- Corresponding author: tuananh{at}ust.hk
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↵5 These authors contributed equally to this work.
Abstract
The Microprocessor complex, consisting of an RNase III DROSHA and the DGCR8 dimer, cleaves primary microRNA transcripts (pri-miRNAs) to initiate microRNA (miRNA) maturation. Pri-miRNAs are stem–loop RNAs, and ∼79% of them contain at least one of the three major and conserved RNA motifs, UG, UGU, and CNNC. We recently demonstrated that the basal UG and apical UGU motifs of pri-miRNAs interact with DROSHA and DGCR8, respectively. They help orient Microprocessor on pri-miRNA in a proper direction in which DROSHA and DGCR8 localize to the basal and apical pri-miRNA junctions, respectively. In addition, CNNC, located at ∼17 nucleotides (nt) from the Microprocessor cleavage site, interacts with SRSF3 (SRp20) to stimulate Microprocessor to process pri-miRNAs. The mechanism underlying this stimulation, however, is unknown. In this study, we discovered that SRSF3 recruits DROSHA to the basal junction in a CNNC-dependent manner, thereby enhancing Microprocessor activity. Furthermore, by generating various pri-miRNA substrates containing CNNC at different locations, we demonstrated that such stimulation only occurs when CNNC is located at ∼17 nt from the Microprocessor cleavage site. Our findings reveal the molecular mechanism of SRSF3 in pri-miRNA processing and support the previously proposed explanation for the highly conserved position of CNNC in SRSF3-enhanced pri-miRNA processing.
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Article is online at http://www.rnajournal.org/cgi/doi/10.1261/rna.065862.118.
- Received January 28, 2018.
- Accepted March 29, 2018.
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