title: mRNA export through an additional cap-binding complex consisting of NCBP1 and NCBP3.
abstract: The flow of genetic information from DNA to protein requires polymerase-II-transcribed RNA characterized by the presence of a 5'-cap. The cap-binding complex (CBC), consisting of the nuclear cap-binding protein (NCBP) 2 and its adaptor NCBP1, is believed to bind all capped RNA and to be necessary for its processing and intracellular localization. Here we show that NCBP1, but not NCBP2, is required for cell viability and poly(A) RNA export. We identify C17orf85 (here named NCBP3) as a cap-binding protein that together with NCBP1 forms an alternative CBC in higher eukaryotes. NCBP3 binds mRNA, associates with components of the mRNA processing machinery and contributes to poly(A) RNA export. Loss of NCBP3 can be compensated by NCBP2 under steady-state conditions. However, NCBP3 becomes pivotal under stress conditions, such as virus infection. We propose the existence of an alternative CBC involving NCBP1 and NCBP3 that plays a key role in mRNA biogenesis.
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Gebhardt
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Habjan
authors.affiliation: Department of Structural Cell Biology, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Benda
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Meiler
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Darya A
authors.initials: DA
authors.lastname: Haas
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Marco Y
authors.identifier: http://orcid.org/0000-0002-9490-2261
authors.initials: MY
authors.lastname: Hein
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Mann
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Bioinformatics Core Facility, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.affiliation: Innate Immunity Laboratory, Max-Planck Institute of Biochemistry, Martinsried, Munich D-82152, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pichlmair
mesh_terms: D000818:Animals; D002470:Cell Survival; D002522:Chlorocebus aethiops; D002853:Chromatography, Liquid; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics* / Q000378:metabolism; D039381:RNA Cap-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D014709:Vero Cells
chemical_list: D039502:Nuclear Cap-Binding Protein Complex; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger