title: Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing.
abstract: The eukaryotic core exosome (CE) is a conserved nine-subunit protein complex important for 3' end trimming and degradation of RNA. In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3'-to-5' exoribonuclease activity. Here we present EM reconstructions of the core and Rrp44-bound exosome complexes. The two-lobed Rrp44 protein binds to the RNase PH domain side of the exosome and buttresses the bottom of the exosome-processing chamber. The Rrp44 C-terminal body part containing an RNase II-type active site is anchored to the exosome through a conserved set of interactions mainly to the Rrp45 and Rrp43 subunit, whereas the Rrp44 N-terminal head part is anchored to the Rrp41 subunit and may function as a roadblock to restrict access of RNA to the active site in the body region. The Rrp44-exosome (RE) architecture suggests an active site sequestration mechanism for strict control of 3' exoribonuclease activity in the RE complex.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. hwwang@lbl.gov
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.forename: Kevin
authors.initials: K
authors.lastname: Callahan
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Bratkowski
authors.forename: J Scott
authors.initials: JS
authors.lastname: Butler
authors.forename: Eva
authors.initials: E
authors.lastname: Nogales
authors.forename: Ailong
authors.initials: A
authors.lastname: Ke
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D005095:Exoribonucleases / Q000378:metabolism; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D012323:RNA Processing, Post-Transcriptional; D034443:RNA Transport; D012331:RNA, Fungal / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000648:ultrastructure; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C542283:DIS3 protein, S cerevisiae