Cyclin-dependent Kinase 9 Links RNA Polymerase II Transcription to Processing of Ribosomal RNA

Autor: Katja Strässer, Kaspar Burger, Michaela Rohrmoser, Anita Gruber-Eber, Markus Kellner, Bastian Mühl, Dirk Eick, Vigo Heissmeyer, Martin Heidemann, Britta Coordes
Rok vydání: 2013
Předmět:
Ribonuclease III
Transcription
Genetic
RNA polymerase II
Biochemistry
DEAD-box RNA Helicases
Mice
03 medical and health sciences
0302 clinical medicine
Piperidines
Transcription (biology)
Cell Line
Tumor
RNA polymerase I
Animals
Humans
RNA
Small Nucleolar
RNA Processing
Post-Transcriptional
RRNA processing
Molecular Biology
RNA polymerase II holoenzyme
030304 developmental biology
Feedback
Physiological
Flavonoids
Mice
Knockout
0303 health sciences
biology
General transcription factor
CDK (Cyclin-dependent Kinase)
Flavopiridol
RNA Polymerase I
RNA Polymerase II
Ribosomal RNA Processing
Small Nucleolar RNA (snoRNA)
Cell Biology
Cyclin-Dependent Kinase 9
Molecular biology
RNA
Ribosomal
Gene Knockdown Techniques
030220 oncology & carcinogenesis
biology.protein
Transcription factor II F
biological phenomena
cell phenomena
and immunity
RNA 3' End Processing
Transcription factor II D
Cell Nucleolus
Zdroj: Journal of Biological Chemistry
J. Biol. Chem. 288, 21173-21183 (2013)
ISSN: 0021-9258
DOI: 10.1074/jbc.m113.483719
Popis: 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.
Databáze: OpenAIRE
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