title: A-kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA synthesis.
abstract: The RNA polymerase I transcription apparatus acquires and integrates the combined information from multiple cellular signalling cascades to regulate ribosome production essential for cell growth and proliferation. In the present study, we show that a subpopulation of A-kinase anchoring protein 95 (AKAP95) targets the nucleolus during interphase and is involved in regulating rRNA production. We show that AKAP95 co-localizes with the nucleolar upstream binding factor, an essential rRNA transcription factor. Similar to other members of the C2 H2 -zinc finger family, we show, using systematic selection and evolution of ligands by exponential enrichment and in vitro binding analysis, that AKAP95 has a preference for GC-rich DNA in vitro, whereas fluorescence recovery after photobleaching analysis reveals AKAP95 to be a highly mobile protein that exhibits RNA polymerase I and II dependent nucleolar trafficking. In line with its GC-binding features, chromatin immunoprecipitation analysis revealed AKAP95 to be associated with ribosomal chromatin in vivo. Manipulation of AKAP95-expression in U2OS cells revealed a reciprocal relationship between the expression of AKAP95 and 47S rRNA. Taken together, our data indicate that AKAP95 is a novel nucleolus-associated protein with a regulatory role on rRNA production.
authors.affiliation: Centre of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Marstad
authors.affiliation: Department of Pathology, Centre for Immune Regulation, Oslo University Hospital Norway, Norway.
authors.forename: Ole Jørgen B
authors.initials: OJ
authors.lastname: Landsverk
authors.affiliation: Centre of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Olaf
authors.initials: O
authors.lastname: Strømme
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Otterlei
authors.affiliation: Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Norway.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
authors.affiliation: Centre of Molecular Inflammation Research (CEMIR), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.|KG Jebsen Centre for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Sundan
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Gaute
authors.initials: G
authors.lastname: Brede
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D012335:RNA, Ribosomal / Q000096:biosynthesis*
chemical_list: D054758:A Kinase Anchor Proteins; C485099:AKAP8 protein, human; D012335:RNA, Ribosomal
keywords: AKAP95; RNA polymerase I; UBF; nucleolus; rRNA