Roberts Douglas N, Wilson Boris, Huff Jason T, Stewart Allen J, Cairns Bradley R
Howard Hughes Medical Institute, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
Mol Cell. 2006 Jun 9;22(5):633-44. doi: 10.1016/j.molcel.2006.04.009.
Nutrient deprivation and various stress conditions repress RNA polymerase III (Pol III) transcription in S. cerevisiae. The signaling pathways that relay stress and nutrient conditions converge on the conserved protein Maf1, but how Maf1 integrates environmental conditions and couples them to transcriptional repression is largely unknown. Here, we demonstrate that Maf1 is phosphorylated in favorable conditions, whereas diverse unfavorable conditions lead to rapid Maf1 dephosphorylation, nuclear localization, physical association of dephosphorylated Maf1 with Pol III, and Maf1 targeting to Pol III-transcribed genes genome wide. Furthermore, Maf1 mutants defective in full dephosphorylation display maf1Delta phenotypes and are compromised for both nuclear localization and Pol III association. Repression conditions also promote TFIIIB-TFIIIC interactions in crosslinked chromatin. Taken together, Maf1 appears to integrate environmental conditions and signaling pathways through its phosphorylation state, with stress leading to dephosphorylation, association with Pol III at target loci, alterations in basal factor interactions, and transcriptional repression.
营养剥夺和各种应激条件会抑制酿酒酵母中的RNA聚合酶III（Pol III）转录。传递应激和营养条件的信号通路汇聚于保守蛋白Maf1，但Maf1如何整合环境条件并将其与转录抑制相耦合在很大程度上尚不清楚。在这里，我们证明Maf1在有利条件下被磷酸化，而各种不利条件会导致Maf1快速去磷酸化、核定位、去磷酸化的Maf1与Pol III的物理结合以及Maf1在全基因组范围内靶向Pol III转录的基因。此外，在完全去磷酸化方面存在缺陷的Maf1突变体表现出Maf1缺失的表型，并且在核定位和与Pol III的结合方面都受到损害。抑制条件还会促进交联染色质中的TFIIIB-TFIIIC相互作用。综上所述，Maf1似乎通过其磷酸化状态整合环境条件和信号通路，应激导致去磷酸化、在靶位点与Pol III结合、基础因子相互作用的改变以及转录抑制。
