title: Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors.
abstract: The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Falk
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Finogenova
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Alle 3, 8000C Aarhus, Denmark.
authors.forename: Mireille
authors.initials: M
authors.lastname: Melko
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Benda
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Alle 3, 8000C Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Lykke-Andersen
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Alle 3, 8000C Aarhus, Denmark.
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
authors.affiliation: Department of Structural Cell Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000378:metabolism; D012326:RNA Splicing; D000072260:RNA Splicing Factors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D021122:Protein Subunits; C000596172:RBM7 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C486348:SF3B2 protein, human; C506699:ZCCHC8 protein, human; D011392:Proline