Chymkowitch Pierre, Nguéa P Aurélie, Aanes Håvard, Robertson Joseph, Klungland Arne, Enserink Jorrit M
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, NO-0379 Oslo, Norway;
Section for Biochemistry and Molecular Biology, The Department of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, NO-0371 Oslo, Norway.
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1039-1044. doi: 10.1073/pnas.1615093114. Epub 2017 Jan 17.
Maintaining cellular homeostasis under changing nutrient conditions is essential for the growth and development of all organisms. The mechanisms that maintain homeostasis upon loss of nutrient supply are not well understood. By mapping the SUMO proteome in Saccharomyces cerevisiae, we discovered a specific set of differentially sumoylated proteins mainly involved in transcription. RNA polymerase III (RNAPIII) components, including Rpc53, Rpc82, and Ret1, are particularly prominent nutrient-dependent SUMO targets. Nitrogen starvation, as well as direct inhibition of the master nutrient response regulator target of rapamycin complex 1 (TORC1), results in rapid desumoylation of these proteins, which is reflected by loss of SUMO at tRNA genes. TORC1-dependent sumoylation of Rpc82 in particular is required for robust tRNA transcription. Mechanistically, sumoylation of Rpc82 is important for assembly of the RNAPIII holoenzyme and recruitment of Rpc82 to tRNA genes. In conclusion, our data show that TORC1-dependent sumoylation of Rpc82 bolsters the transcriptional capacity of RNAPIII under optimal growth conditions.
在不断变化的营养条件下维持细胞内稳态对所有生物体的生长和发育至关重要。营养供应缺失时维持内稳态的机制尚未完全了解。通过绘制酿酒酵母中的SUMO蛋白质组图谱,我们发现了一组特定的差异SUMO化蛋白质,主要参与转录过程。RNA聚合酶III(RNAPIII)的组分,包括Rpc53、Rpc82和Ret1,是特别显著的营养依赖性SUMO靶标。氮饥饿以及对主要营养反应调节因子雷帕霉素复合物1(TORC1)靶标的直接抑制,会导致这些蛋白质快速去SUMO化,这在tRNA基因处SUMO的缺失中得到体现。特别是Rpc82的TORC1依赖性SUMO化对于强大的tRNA转录是必需的。从机制上讲,Rpc82的SUMO化对于RNAPIII全酶的组装以及Rpc82募集到tRNA基因很重要。总之,我们的数据表明,在最佳生长条件下,Rpc82的TORC1依赖性SUMO化增强了RNAPIII的转录能力。