Lindquist S, Krobitsch S, Li L, Sondheimer N
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Philos Trans R Soc Lond B Biol Sci. 2001 Feb 28;356(1406):169-76. doi: 10.1098/rstb.2000.0762.
Our work supports the hypothesis that a protein can serve as an element of genetic inheritance. This protein-only mechanism of inheritance is propagated in much the same way as hypothesized for the transmission of the protein-only infectious agent in the spongiform encephalopathies; hence these protein factors have been called yeast prions. Our work has focused on [PSI(+)], a dominant cytoplasmically inherited factor that alters translational fidelity. This change in translation is produced by a self-perpetuating change in the conformation of the translation-termination factor, Sup35. Most recently, we have determined that new elements of genetic inheritance can be created by deliberate genetic engineering, opening prospects for new methods of manipulating heredity. We have also uncovered evidence that other previously unknown elements of protein-based inheritance are encoded in the yeast genome. Finally, we have begun to use yeast as a model system for studying human protein folding diseases, such as Huntington's disease. Proteins responsible for some of these diseases have properties uncannily similar to those that produce protein-based mechanisms of inheritance.
我们的研究工作支持了一种假说，即蛋白质可以作为遗传继承的一个要素。这种仅由蛋白质构成的遗传机制的传播方式，与在海绵状脑病中传播仅由蛋白质构成的感染因子的假说非常相似；因此，这些蛋白质因子被称为酵母朊病毒。我们的研究工作集中在[PSI(+)]上，这是一种显性的细胞质遗传因子，它会改变翻译保真度。这种翻译变化是由翻译终止因子Sup35的构象发生自我延续的变化所产生的。最近，我们确定可以通过有意的基因工程创造出新的遗传继承要素，为操纵遗传的新方法开辟了前景。我们还发现有证据表明，酵母基因组中编码了其他以前未知的基于蛋白质的遗传要素。最后，我们已开始将酵母用作研究人类蛋白质折叠疾病（如亨廷顿舞蹈症）的模型系统。导致其中一些疾病的蛋白质具有与那些产生基于蛋白质的遗传机制的蛋白质极为相似的特性。
