Aksenova Anna, Muñoz Iván, Volkov Kirill, Ariño Joaquín, Mironova Ludmila
Department of Genetics, St. Petersburg State University, 199034, St. Petersburg, Russia.
Genes Cells. 2007 Apr;12(4):435-45. doi: 10.1111/j.1365-2443.2007.01064.x.
The efficiency of stop codons read-through in yeast is controlled by multiple interactions of genetic and epigenetic factors. In this study, we demonstrate the participation of the Hal3-Ppz1 protein complex in regulation of read-through efficiency and manifestation of non-Mendelian anti-suppressor determinant [ISP(+)]. Over-expression of HAL3 in [ISP(+)] strain causes nonsense suppression, whereas its inactivation displays as anti-suppression of sup35 mutation in [isp(-)] strain. [ISP(+)] strains carrying hal3Delta deletion cannot be cured from [ISP(+)] in the presence of GuHCl. Since Hal3p is a negative regulatory subunit of Ppz1 protein phosphatase, consequences of PPZ1 over-expression and deletion are opposite to those of HAL3. The observed effects are mediated by the catalytic function of Ppz1 and are probably related to the participation of Ppz1 in regulation of eEF1Balpha elongation factor activity. Importantly, [ISP(+)] status of yeast strains is determined by fluctuation in Hal3p level, since [ISP(+)] strains have less Hal3p than their [isp(-)] derivatives obtained by GuHCl treatment. A model considering epigenetic (possibly prion) regulation of Hal3p amount as a mechanism underlying [ISP(+)] status of yeast cell is suggested.
酵母中终止密码子通读的效率受遗传和表观遗传因素的多重相互作用控制。在本研究中，我们证明了Hal3-Ppz1蛋白复合物参与通读效率的调节以及非孟德尔抗抑制决定因素[ISP(+)]的表现。在[ISP(+)]菌株中过表达HAL3会导致无义抑制，而其失活则表现为[isp(-)]菌株中sup35突变的抗抑制。携带hal3Delta缺失的[ISP(+)]菌株在GuHCl存在下无法从[ISP(+)]中治愈。由于Hal3p是Ppz1蛋白磷酸酶的负调节亚基，PPZ1过表达和缺失的后果与HAL3相反。观察到的效应由Ppz1的催化功能介导，可能与Ppz1参与eEF1Balpha延伸因子活性的调节有关。重要的是，酵母菌株的[ISP(+)]状态由Hal3p水平的波动决定，因为[ISP(+)]菌株的Hal3p比通过GuHCl处理获得的[isp(-)]衍生物少。提出了一个模型，将Hal3p量的表观遗传（可能是朊病毒）调节视为酵母细胞[ISP(+)]状态的潜在机制。
