title: Cyclin-dependent kinase 9 links RNA polymerase II transcription to processing of ribosomal RNA.
abstract: Ribosome biogenesis is a process required for cellular growth and proliferation. Processing of ribosomal RNA (rRNA) is highly sensitive to flavopiridol, a specific inhibitor of cyclin-dependent kinase 9 (Cdk9). Cdk9 has been characterized as the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Here we studied the connection between RNAPII transcription and rRNA processing. We show that inhibition of RNAPII activity by α-amanitin specifically blocks processing of rRNA. The block is characterized by accumulation of 3' extended unprocessed 47 S rRNAs and the entire inhibition of other 47 S rRNA-specific processing steps. The transcription rate of rRNA is moderately reduced after inhibition of Cdk9, suggesting that defective 3' processing of rRNA negatively feeds back on RNAPI transcription. Knockdown of Cdk9 caused a strong reduction of the levels of RNAPII-transcribed U8 small nucleolar RNA, which is essential for 3' rRNA processing in mammalian cells. Our data demonstrate a pivotal role of Cdk9 activity for coupling of RNAPII transcription with small nucleolar RNA production and rRNA processing.
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Kaspar
authors.initials: K
authors.lastname: Burger
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Mühl
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Rohrmoser
authors.affiliation: Gene Center and Department of Biochemistry, Center for Integrated Protein Science Munich, Ludwig Maximilians University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany, and.
authors.forename: Britta
authors.initials: B
authors.lastname: Coordes
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heidemann
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kellner
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Gruber-Eber
authors.affiliation: Institute of Molecular Immunology, Helmholtz Center Munich, Marchioninistrasse 25, 81377 Munich, Germany.
authors.forename: Vigo
authors.initials: V
authors.lastname: Heissmeyer
authors.affiliation: Gene Center and Department of Biochemistry, Center for Integrated Protein Science Munich, Ludwig Maximilians University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany, and.
authors.forename: Katja
authors.initials: K
authors.lastname: Strässer
authors.affiliation: From the Department of Molecular Epigenetics, Helmholtz Center Munich, Center for Integrated Protein Science Munich, Marchioninistrasse 25, 81377 Munich, Germany,. Electronic address: eick@helmholtz-muenchen.de.
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000187:drug effects / Q000201:enzymology; D042863:Cyclin-Dependent Kinase 9 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D026721:RNA 3' End Processing / Q000187:drug effects / Q000235:genetics; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012335:RNA, Ribosomal / Q000235:genetics*; D020537:RNA, Small Nucleolar / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D005419:Flavonoids; D010880:Piperidines; D012335:RNA, Ribosomal; D020537:RNA, Small Nucleolar; C077990:alvocidib; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: CDK (Cyclin-dependent Kinase); Flavopiridol; RNA Polymerase I; RNA Polymerase II; Ribosomal RNA Processing; Small Nucleolar RNA (snoRNA)