期刊
ONCOTARGET
卷 8, 期 63, 页码 106587-106597出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22540
关键词
RNA-binding protein; RNA-binding pocket; nuclear magnetic resonance; backbone assignment; Musashi
资金
- National Institutes of Health [R01 CA178831, CA191785]
- NIH COBRE-PSF at KU [P30 GM110761]
- Department of Defense Breast Cancer Research Program Breakthrough Level II grant [BC151845]
- Kansas Bioscience Authority Rising Star Award
- CDMRP [893240, BC151845] Funding Source: Federal RePORTER
RNA-binding protein Musashi-2 (MSI2) is a key regulator in stem cells, it is over-expressed in a variety of cancers and its higher expression is associated with poor prognosis. Like Musashi-1, it contains two N-terminal RRMs (RNA-recognition Motifs, also called RBDs (RNA-binding Domains)), RRM1 and RRM2, which mediate the binding to their target mRNAs. Previous studies have obtained the three-dimensional structures of the RBDs of Musashi-1 and the RBD1: RNA complex. Here we show the binding of MSI2-RRM1 to a 15nt Numb RNA in Fluorescence Polarization assay and time resolved Fluorescence Resonance Energy Transfer assay. Using nuclear magnetic resonance (NMR) spectroscopy we assigned the backbone resonances of MSI2-RRM1, and characterized the direct interaction of RRM1 to Numb RNA r(GUAGU). Our NMR titration and structure modeling studies showed that MSI2-RRM1 and MSI1-RBD1 have similar RNA binding events and binding pockets. This work adds significant information to MSI2-RRM1 structure and RNA binding pocket, and contributes to the development of MSI2 specific and MSI1/MSI2 dual inhibitors.
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