title: Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation.
abstract: 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.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673.
authors.forename: Donghui
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder CO 80303, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Muhlrad
authors.affiliation: 1] European Molecular Biology Laboratory, 6 rue Jules Horowitz, BP 181, 38042, Grenoble, France [2] Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMI 3265, 6 rue Jules Horowitz, 38042 Grenoble Cedex 9, France.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Bowler
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673.
authors.forename: Shimin
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang 310000, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, University of Colorado, Boulder, Boulder CO 80303, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Parker
authors.affiliation: 1] Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673 [2] Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang 310000, China [3] Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Song
mesh_terms: D018360:Crystallography, X-Ray; D016296:Mutagenesis; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012315:RNA Caps / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C487374:LSM3 protein, S cerevisiae; C493532:Lsm2 protein, S cerevisiae; C103266:PAT1 protein, S cerevisiae; D012315:RNA Caps; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA