Donghui Wu1, Denise Muhlrad2, Matthew W Bowler3,4, Shimin Jiang1, Zhou Liu5, Roy Parker2 and Haiwei Song1,5,6*
1 Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673.
2 Department of Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder CO 80303, USA.
3 European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042, Grenoble, France.
4 Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France.
5 Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou, China.
6 Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543
* Correspondence should be addressed to Haiwei Song (email@example.com)
Published online in Cell Research on 19 November 2013.
The evolutionarily conserved Lsm1-7-Pat1 complex is the most critical activator of mRNA decapping in eukaryotic cells and plays roles in normal decay, ARE-mediated decay, and miRNA silencing, yet how Pat1 interacts with the Lsm1-7 complex is unknown. Here, we show that the Lsm2 and Lsm3 bridge the interaction between the C-terminus of Pat1 (Pat1C) and the Lsm1-7 complex. The Lsm2-3-Pat1C complex and the Lsm1-7-Pat1C complex stimulate decapping in vitro to a similar extent and exhibit similar RNA binding preference. The crystal structure of the Lsm2-3-Pat1C complex shows that Pat1C binds to Lsm2-3 to form an asymmetric complex with three Pat1C molecules surrounding a heptameric ring formed by Lsm2-3. Structure-based mutagenesis revealed the interaction of Pat1C with Lsm2-3 affects decapping in vivo. Based on the structure of Lsm2-3-Pat1C, a model of Lsm1-7-Pat1 complex is constructed and how RNA binds to this complex is discussed.
Figure Legend: Eukaryotic mRNA decapping activator Lsm2-3-Pat1 complex consists of three Pat1 molecules
and seven-membered Lsm ring structure, arranged in an asymmetrical manner.
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