Myb-binding protein 1a (Mybbp1a) regulates levels and processing of pre-ribosomal RNA.
Ribosomal RNA gene transcription, co-transcriptional processing, and ribosome biogenesis are highly coordinated processes that are tightly regulated during cell growth. In this study we discovered that Mybbp1a is associated with both the RNA polymerase I complex and the ribosome biogenesis machinery. Using a reporter assay that uncouples transcription and RNA processing, we show that Mybbp1a represses rRNA gene transcription. In addition, overexpression of the protein reduces RNA polymerase I loading on endogenous rRNA genes as revealed by chromatin immunoprecipitation experiments. Accordingly, depletion of Mybbp1a results in an accumulation of the rRNA precursor in vivo but surprisingly also causes growth arrest of the cells. This effect can be explained by the observation that the modulation of Mybbp1a protein levels results in defects in pre-rRNA processing within the cell. Therefore, the protein may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes.
Biochemistry Center Regensburg, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
Julia
J
Hochstatter
Michael
M
Hölzel
Michaela
M
Rohrmoser
Lothar
L
Schermelleh
Heinrich
H
Leonhardt
Rebecca
R
Keough
Thomas J
TJ
Gonda
Axel
A
Imhof
Dirk
D
Eick
Gernot
G
Längst
Attila
A
Németh
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D012270:Ribosomes / Q000378:metabolism*; D014157:Transcription Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C491719:MYBBP1A protein, human; C110421:Mybbp1a protein, mouse; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D012318:RNA Polymerase I