title: Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate.
abstract: The nuclear cap-binding complex (CBC) stimulates processing reactions of capped RNAs, including their splicing, 3'-end formation, degradation, and transport. CBC effects are particular for individual RNA families, but how such selectivity is achieved remains elusive. Here, we analyze three main CBC partners known to impact different RNA species. ARS2 stimulates 3'-end formation/transcription termination of several transcript types, ZC3H18 stimulates degradation of a diverse set of RNAs, and PHAX functions in pre-small nuclear RNA/small nucleolar RNA (pre-snRNA/snoRNA) transport. Surprisingly, these proteins all bind capped RNAs without strong preferences for given transcripts, and their steady-state binding correlates poorly with their function. Despite this, PHAX and ZC3H18 compete for CBC binding and we demonstrate that this competitive binding is functionally relevant. We further show that CBC-containing complexes are short lived in vivo, and we therefore suggest that RNA fate involves the transient formation of mutually exclusive CBC complexes, which may only be consequential at particular checkpoints during RNA biogenesis.
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, Bldg. 1130, 8000 Aarhus C, Denmark; Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Giacometti
authors.affiliation: Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France.
authors.forename: Nour El Houda
authors.initials: NEH
authors.lastname: Benbahouche
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, Bldg. 1130, 8000 Aarhus C, Denmark.
authors.forename: Michal
authors.initials: M
authors.lastname: Domanski
authors.affiliation: Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Robert
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, Bldg. 1130, 8000 Aarhus C, Denmark.
authors.forename: Nicola
authors.initials: N
authors.lastname: Meola
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, Bldg. 1130, 8000 Aarhus C, Denmark.
authors.forename: Michal
authors.initials: M
authors.lastname: Lubas
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Bukenborg
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.affiliation: Grenoble Outstation, European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble, France.
authors.forename: Wiebke M
authors.initials: WM
authors.lastname: Schulze
authors.affiliation: Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Verheggen
authors.affiliation: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4, UK. Electronic address: gkudla@gmail.com.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kudla
authors.affiliation: Centre for mRNP Biogenesis and Metabolism, Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, Bldg. 1130, 8000 Aarhus C, Denmark. Electronic address: thj@mbg.au.dk.
authors.forename: Torben Heick
authors.initials: TH
authors.lastname: Jensen
authors.affiliation: Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France. Electronic address: edouard.bertrand@igmm.cnrs.fr.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bertrand
mesh_terms: D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D039502:Nuclear Cap-Binding Protein Complex / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger; D012313:RNA; D012319:RNA Polymerase II
keywords: CBC; CBC interacting proteins; CLIP; FRAP; RNA cap; RNA decay; RNA fate decisions; RNA transport; cap