Xuhua Tang1, Sakshibeedu R Bharath1, Shunfu Piao1, Vanessa Qianmin Tan1, Matthew W. Bowler2,3 and Haiwei Song1,4
1 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore
2 European Molecular Biology Laboratory, Grenoble Outstation, 71 avenue des Martyrs, CS 90181F 38042 Grenoble, France
3 Unit of Virus Host-Cell Interactions, Univ. Grenoble Alpes-EMBL-CNRS, 71 avenue des Martyrs, CS 90181 F-38042 Grenoble, France
4 Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543, Singapore
Correspondence should be addressed to H.S. (firstname.lastname@example.org)
Published online ahead of print in Cell Research on 11 November 2016.
Gemin5 confers the stringent specificity of the SMN complex towards pre-snRNAs for the biogenesis of snRNPs. Here we report the structures of WD40 domain of Gemin5 in complex with the m7GpppG cap and the Sm site RNA (nt 118-127 in pre-U4 snRNA). Gemin5 specifically recognizes the Sm RNA and the m7GpppG cap through its first and second β-propellers, respectively. This dual-recognition mechanism ensures only the correct snRNAs assembled on the Sm core, thereby preventing illicit Sm core formation. Our results provide a framework for further elucidating how Gemin5 delivers pre-snRNAs to the SMN complex for the biogenesis of snRNP.
Figure. 1. Specific recognition of m7GpppG cap and the Sm site of pre-snRNA by Gemin5-WD. (A) Overall structure of Gemin5-WD in complex with m7GpppG cap. WD1 and WD2 of Gemin5-WD are shown in light blue and green, respectively. m7GpppG cap is shown in purple. (B) Electrostatic surface potential of Gemin5-WD complexed with Sm RNA. RNA used in the study is shown with specificity determining nucleotides in red and those not observed in density in grey. (C) The specificity determinants of Sm RNA for Gemin5 recognition were examined by fluorescence anisotropy.
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