title: The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome.
abstract: The eukaryotic RNA exosome is an essential, multi-subunit complex that catalyzes RNA turnover, maturation, and quality control processes. Its non-catalytic donut-shaped core includes 9 subunits that associate with the 3' to 5' exoribonucleases Rrp6, and Rrp44/Dis3, a subunit that also catalyzes endoribonuclease activity. Although recent structures and biochemical studies of RNA bound exosomes from S. cerevisiae revealed that the Exo9 central channel guides RNA to either Rrp6 or Rrp44 using partially overlapping and mutually exclusive paths, several issues related to RNA recruitment remain. Here, we identify activities for the highly basic Rrp6 C-terminal tail that we term the 'lasso' because it binds RNA and stimulates ribonuclease activities associated with Rrp44 and Rrp6 within the 11-subunit nuclear exosome. Stimulation is dependent on the Exo9 central channel, and the lasso contributes to degradation and processing activities of exosome substrates in vitro and in vivo. Finally, we present evidence that the Rrp6 lasso may be a conserved feature of the eukaryotic RNA exosome.
authors.affiliation: Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Wasmuth
authors.affiliation: Structural Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA limac@mskcc.org.|Howard Hughes Medical Institute, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lima
mesh_terms: D005095:Exoribonucleases / Q000737:chemistry / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability
chemical_list: D012313:RNA; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C551543:DIS3 protein, human; C077044:EXOSC10 protein, human