Hochstatter J, Holzel M, Rohrmoser M, Schermelleh L, Leonhardt H, Keough R, Gonda TJ, Imhof A, Eick D, Langst G, Nemeth A
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 (RNA Pol 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 Pol 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 causes also 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 (rDNA) transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes.