Biochemistry Center Regensburg, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
J Biol Chem. 2012 Jul 13;287(29):24365-77. doi: 10.1074/jbc.M111.303719. Epub 2012 May 29.
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.
核糖体 RNA 基因转录、共转录加工和核糖体生物发生是高度协调的过程，在细胞生长过程中受到严格调控。在这项研究中，我们发现 Mybbp1a 与 RNA 聚合酶 I 复合物和核糖体生物发生机制都有关联。我们使用一种分离转录和 RNA 加工的报告基因检测实验，表明 Mybbp1a 抑制 rRNA 基因转录。此外，过表达该蛋白会导致 RNA 聚合酶 I 在内源 rRNA 基因上的加载减少，这一点通过染色质免疫沉淀实验得到了揭示。因此，Mybbp1a 的耗竭会导致 rRNA 前体在体内积累，但令人惊讶的是，这也会导致细胞生长停滞。这种效应可以通过以下观察结果来解释：Mybbp1a 蛋白水平的调节会导致细胞内 pre-rRNA 加工缺陷。因此，该蛋白可能在 rRNA 代谢中发挥双重作用，可能将核糖体 DNA 转录和 pre-rRNA 加工联系和协调起来，以实现核糖体的高效合成。
