A conserved three-nucleotide core motif defines Musashi RNA binding specificity
Authors
Zearfoss, Nancy R.Deveau, Laura M.
Clingman, Carina C.
Schmidt, Eric
Johnson, Emily S.
Massi, Francesca
Ryder, Sean P.
Student Authors
Carina C. ClingmanUMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2014-12-19Keywords
Algorithms; Animals; Base Sequence; Binding Sites; Conserved Sequence; Drosophila Proteins; Fluorescence Polarization; Humans; Kinetics; Magnetic Resonance Spectroscopy; Mice; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Nucleotide Motifs; Protein Binding; RNA; RNA-Binding Proteins; Sequence Homology, Nucleic AcidBiochemistry
Genetics and Genomics
Molecular Biology
Metadata
Show full item recordAbstract
Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside of this motif have a limited contribution to binding free energy. For mouse MSI1, recognition is determined by the first of the two RRM domains. The second RRM adds affinity but does not contribute to binding specificity. In contrast, the recognition element for Drosophila MSI is more extensive than the mouse homolog, suggesting functional divergence. The short nature of the binding determinant suggests that protein-RNA affinity alone is insufficient to drive target selection by MSI family proteins.Source
J Biol Chem. 2014 Dec 19;289(51):35530-41. doi: 10.1074/jbc.M114.597112. Epub 2014 Nov 3. Link to article on publisher's siteDOI
10.1074/jbc.M114.597112Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33372PubMed ID
25368328Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M114.597112