title: The human cap-binding complex is functionally connected to the nuclear RNA exosome.
abstract: Nuclear processing and quality control of eukaryotic RNA is mediated by the RNA exosome, which is regulated by accessory factors. However, the mechanism of exosome recruitment to its ribonucleoprotein (RNP) targets remains poorly understood. Here we report a physical link between the human exosome and the cap-binding complex (CBC). The CBC associates with the ARS2 protein to form CBC-ARS2 (CBCA) and then further connects, together with the ZC3H18 protein, to the nuclear exosome targeting (NEXT) complex, thus forming CBC-NEXT (CBCN). RNA immunoprecipitation using CBCN factors as well as the analysis of combinatorial depletion of CBCN and exosome components underscore the functional relevance of CBC-exosome bridging at the level of target RNA. Specifically, CBCA suppresses read-through products of several RNA families by promoting their transcriptional termination. We suggest that the RNP 5' cap links transcription termination to exosomal RNA degradation through CBCN.
authors.affiliation: 1] Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark. [2].
authors.forename: Peter Refsing
authors.initials: PR
authors.lastname: Andersen
authors.forename: Michal
authors.initials: M
authors.lastname: Domanski
authors.forename: Maiken S
authors.initials: MS
authors.lastname: Kristiansen
authors.forename: Helena
authors.initials: H
authors.lastname: Storvall
authors.forename: Evgenia
authors.initials: E
authors.lastname: Ntini
authors.forename: Celine
authors.initials: C
authors.lastname: Verheggen
authors.forename: Aleks
authors.initials: A
authors.lastname: Schein
authors.forename: Jakob
authors.initials: J
authors.lastname: Bunkenborg
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Marie
authors.initials: M
authors.lastname: Hallais
authors.forename: Rickard
authors.initials: R
authors.lastname: Sandberg
authors.forename: Anthony
authors.initials: A
authors.lastname: Hyman
authors.forename: John
authors.initials: J
authors.lastname: LaCava
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rout
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
mesh_terms: D063326:Exosome Multienzyme Ribonuclease Complex / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D039502:Nuclear Cap-Binding Protein Complex / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D020871:RNA Stability; D061806:Transcription Termination, Genetic
chemical_list: D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; C527299:SRRT protein, human; D063326:Exosome Multienzyme Ribonuclease Complex