Yu Feifei, Imamura Yuko, Ueno Masaru, Suzuki Sho W, Ohsumi Yoshinori, Yukawa Masashi, Tsuchiya Eiko
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530, Japan.
Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):1248-1253. doi: 10.1016/j.bbrc.2015.07.114. Epub 2015 Jul 26.
The yeast RSC, an ATP-dependent chromatin-remodeling complex, is essential for mitotic and meiotic growth. There are two distinct isoforms of this complex defined by the presence of either Rsc1 or Rsc2; however, the functional differences between these complexes are unclear. Here we show that the RSC complex containing Rsc1, but not Rsc2, functions in autophagy induction. Rsc1 was required not only for full expression of ATG8 mRNA but also for maintenance of Atg8 protein stability. Interestingly, decreased autophagic activity and Atg8 protein stability in rsc1Δ cells, but not the defect in ATG8 mRNA expression, were partially suppressed by deletion of TOR1. In addition, we found that rsc1Δ impaired the binding between the Rho GTPase Rho1 and the TORC1-specific component Kog1, which is required for down-regulation of TORC1 activity. These results suggest that the Rsc1-containing RSC complex plays dual roles in the proper induction of autophagy: 1) the transcriptional activation of autophagy-related genes independent of the TORC1 pathway and 2) the inactivation of TORC1, possibly through enhancement of Rho1-Kog1 binding.
酵母RSC是一种依赖ATP的染色质重塑复合体,对有丝分裂和减数分裂生长至关重要。该复合体有两种不同的亚型,由Rsc1或Rsc2的存在来定义;然而,这些复合体之间的功能差异尚不清楚。在这里,我们表明含有Rsc1而非Rsc2的RSC复合体在自噬诱导中起作用。Rsc1不仅是ATG8 mRNA充分表达所必需的,也是维持Atg8蛋白稳定性所必需的。有趣的是,rsc1Δ细胞中自噬活性和Atg8蛋白稳定性的降低,而非ATG8 mRNA表达的缺陷,通过缺失TOR1得到部分抑制。此外,我们发现rsc1Δ损害了Rho GTP酶Rho1与TORC1特异性组分Kog1之间的结合,而这是TORC1活性下调所必需的。这些结果表明,含有Rsc1的RSC复合体在自噬的适当诱导中发挥双重作用:1)独立于TORC1途径的自噬相关基因的转录激活;2)TORC1的失活,可能是通过增强Rho1-Kog1的结合来实现。