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Burger, K. ; Mühl, B. ; Rohrmoser, M. ; Coordes, B.* ; Heidemann, M. ; Kellner, M. ; Gruber-Eber, A. ; Heissmeyer, V. ; Strässer, K.* ; Eick, D.

Cyclin-dependent kinase 9 links RNA polymerase II transcription to processing of ribosomal RNA.

J. Biol. Chem. 288, 21173-21183 (2013)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords CDK (Cyclin-dependent Kinase); Flavopiridol; RNA Polymerase I; RNA Polymerase II; Ribosomal RNA Processing; Small Nucleolar RNA (snoRNA); Small Nucleolar Rnas ; Messenger-rna ; Saccharomyces-cerevisiae ; Box C/d ; P-tefb ; Preribosomal Rna ; Terminal Domain ; H/aca Snornas ; In-vivo ; Biogenesis
Language english
Publication Year 2013
HGF-reported in Year 2013
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Journal Journal of Biological Chemistry, The
Quellenangaben Volume: 288, Issue: 29, Pages: 21173-21183 Article Number: , Supplement: ,
Publisher American Society for Biochemistry and Molecular Biology
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
Institute of Molecular Immunology (IMI)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501490-001
G-501792-001
G-501793-001
G-501400-006
PubMed ID 23744076
DOI 10.1074/jbc.M113.483719
WOS ID WOS:000322014400037
Scopus ID 84880529732
Erfassungsdatum 2013-08-02
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