title: The C-terminal alpha-alpha superhelix of Pat is required for mRNA decapping in metazoa.
abstract: Pat proteins regulate the transition of mRNAs from a state that is translationally active to one that is repressed, committing targeted mRNAs to degradation. Pat proteins contain a conserved N-terminal sequence, a proline-rich region, a Mid domain and a C-terminal domain (Pat-C). We show that Pat-C is essential for the interaction with mRNA decapping factors (i.e. DCP2, EDC4 and LSm1-7), whereas the P-rich region and Mid domain have distinct functions in modulating these interactions. DCP2 and EDC4 binding is enhanced by the P-rich region and does not require LSm1-7. LSm1-7 binding is assisted by the Mid domain and is reduced by the P-rich region. Structural analysis revealed that Pat-C folds into an alpha-alpha superhelix, exposing conserved and basic residues on one side of the domain. This conserved and basic surface is required for RNA, DCP2, EDC4 and LSm1-7 binding. The multiplicity of interactions mediated by Pat-C suggests that certain of these interactions are mutually exclusive and, therefore, that Pat proteins switch decapping partners allowing transitions between sequential steps in the mRNA decapping pathway.
authors.affiliation: Department of Biochemistry, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors.forename: Joerg E
authors.initials: JE
authors.lastname: Braun
authors.forename: Felix
authors.initials: F
authors.lastname: Tritschler
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Haas
authors.forename: Cátia
authors.initials: C
authors.lastname: Igreja
authors.forename: Vincent
authors.initials: V
authors.lastname: Truffault
authors.forename: Oliver
authors.initials: O
authors.lastname: Weichenrieder
authors.forename: Elisa
authors.initials: E
authors.lastname: Izaurralde
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; C103266:PAT1 protein, S cerevisiae; C526510:PATL1 protein, human; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins