Volume 24, No 2, Feb 2014

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 24 Issue 2, February 2014: 233-246   |  Open Access

ORIGINAL ARTICLES

Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation

Donghui Wu¹, Denise Muhlrad², Matthew W Bowler^3,4, Zhou Liu⁵, Roy Parker² and Haiwei Song^1,5,6

¹Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673
²Department of Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder CO 80303, USA
³European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042, Grenoble, France
⁴Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France
⁵Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang 310000, China
⁶Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543 Correspondence: Haiwei Song, Tel: +65 65869700(haiwei@imcb.a-star.edu.sg)

The evolutionarily conserved Lsm1-7-Pat1 complex is the most critical activator of mRNA decapping in eukaryotic cells and plays many roles in normal decay, AU-rich element-mediated decay, and miRNA silencing, yet how Pat1 interacts with the Lsm1-7 complex is unknown. Here, we show that 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 importance of Lsm2-3-Pat1C interactions in decapping activation 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.

10.1038/cr.2013.152

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