mRNA export through an additional cap-binding complex consisting of NCBP1 and NCBP3

• Published in: Nature communications Vol. 6; no. 1; p. 8192
• Main Authors: Gebhardt, Anna, Habjan, Matthias, Benda, Christian, Meiler, Arno, Haas, Darya A., Hein, Marco Y., Mann, Angelika, Mann, Matthias, Habermann, Bianca, Pichlmair, Andreas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.09.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 14/19; 38/109; 38/32; 38/89; 38/91; 42/70; 631/337/1645/2052; 631/45/612/1230; 631/80/86; 82/51; 82/58; Animals; Cap-binding protein; Cell Survival; Chlorocebus aethiops; Chromatography, Liquid; Deoxyribonucleic acid; DNA; DNA-directed RNA polymerase; Eukaryotes; Exports; Fluorescent Antibody Technique; Gene Knockdown Techniques; HeLa Cells; Humanities and Social Sciences; Humans; Immunoprecipitation; In Situ Hybridization, Fluorescence; Localization; Macrophages - metabolism; Mice; mRNA; mRNA processing; multidisciplinary; NIH 3T3 Cells; Nuclear Cap-Binding Protein Complex - genetics; Nuclear Cap-Binding Protein Complex - metabolism; Polyadenine; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA Cap-Binding Proteins - genetics; RNA Cap-Binding Proteins - metabolism; RNA transport; RNA, Messenger - metabolism; Science; Science (multidisciplinary); Tandem Mass Spectrometry; Vero Cells; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9192

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. The processing of RNAs transcribed by RNA polymerase II requires a cap-binding complex (CBC), consisting of NCBP1 and NCBP2. Here, the authors report an alternative CBC formed by NCBP1 and a previously uncharacterized protein, NCBP3 that is critical for RNA processing under cellular stress conditions.