Mutually Exclusive CBC-Containing Complexes Contribute to RNA Fate
Simone Giacometti,
Nour El Houda Benbahouche,
Michal Domanski,
Marie-Cécile Robert,
Nicola Meola,
Michal Lubas,
Jakob Bukenborg,
Jens S. Andersen,
Wiebke M. Schulze,
Celine Verheggen,
Grzegorz Kudla,
Torben Heick Jensen,
Edouard Bertrand
Affiliations
Simone Giacometti
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
Nour El Houda Benbahouche
Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France
Michal Domanski
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
Marie-Cécile Robert
Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France
Nicola Meola
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
Michal Lubas
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
Jakob Bukenborg
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Jens S. Andersen
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
Wiebke M. Schulze
Grenoble Outstation, European Molecular Biology Laboratory, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble, France
Celine Verheggen
Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France
Grzegorz Kudla
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4, UK
Torben Heick Jensen
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
Edouard Bertrand
Unité Mixte de Recherche 5535, Institut de Génétique Moléculaire de Montpellier, CNRS and Montpellier University, 34293 Montpellier, France
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.
