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

作　　者：Donghui Wu Denise Muhlrad Matthew W Bowler Shimin Jiang Zhou Liu Roy Parker Haiwei Song 

机构地区：[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, Zhejiang 310000, China [6]Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543

出　　处：《Cell Research》2014年第2期233-246,共14页细胞研究（英文版）

基　　金：We thank the beamline scientists at ID14-4 and ID23-1 （ESRF, France）, PXI （SLS, Switzerland）, BL13B1 （NSRRC, Taiwan） and BL17U （SSRF, Shanghai, China） for assistance and access to syn- chrotron radiation facilities. This work was financially supported by the Agency for Science, Technology and Research in Singapore （HS） and partly by the National Natural Science Foundation of China （31270816） and Zhejiang Provincial Natural Science Fu- oundation of China （LZ 12C05001）.

摘　　要：The evolutionarily conserved Lsml-7-Patl 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 Patl interacts with the Lsml-7 complex is unknown. Here, we show that Lsm2 and Lsm3 bridge the interaction between the C-terminus of Patl （PatlC） and the Lsml-7 complex. The Lsm2-3-PatlC complex and the Lsml-7-PatlC complex stimulate decapping in vitro to a similar extent and exhibit similar RNA-binding preference. The crystal structure of the Lsm2-3-PatlC complex shows that PatlC binds to Lsm2-3 to form an asymmetric complex with three PatlC molecules surrounding a heptameric ring formed by Lsm2-3. Structure-based mutagenesis revealed the importance of Lsm2-3-PatlC interactions in decapping activation in vivo. Based on the structure of Lsm2-3-PatlC, a model of Lsml-7-Patl complex is constructed and how RNA binds to this complex is discussed.

关 键 词：mRNA decay decapping activation LSM Patl x-ray crystallography 

分 类 号：Q945.11[生物学—植物学] Q26