Yeast prions influence the appearance and stability of other yeast prions.

摘要

Proteins that can adopt either a normal or self-propagating form were first conceptualized to explain a disease in sheep (‘scrapie’) whose infectious agent was resistant to traditional methods of destroying nucleic acid based pathogens. Since the infectious material was primarily composed of protein, the agent was called a prion (short for proteinaceous infectious particle). Later, two traits in yeast, [URE3] and [PSI+], were also proposed to propagate through infectious protein conformations.; A study of the interactions among yeast prions reveals that prions affect the appearance and stability of other prions. First, a third yeast prion, [PIN+], is identified as a form of the Rnq1 protein. The presence of any one of the three yeast prions causes the more frequent appearance of any other yeast prion, except the that presence of [PSI+] inhibits the appearance of [ URE3]. Variants of the [PIN+] prion allow for different amounts of [PSI+] and [URE3] appearance upon overexpression of SUP35 and URE2, respectively. In addition, one type of [ PIN+] variant has an extremely concentrated in vivo Rnq1 aggregate and profoundly decreases the stability of weak [PSI+] variants, while another type has more distributed in vivo Rnq1 aggregates and does not affect various [PSI+]-related phenotypes. Two mechanisms of action are proposed to explain how prions influence the appearance and stability other prions. The prion domain of SUP35 is redefined as the minimal fragment necessary to maintain different variants of [ PSI+] for the following reasons. First, the minimal prion domain of SUP35 is found to be larger than previously determined. Second, fragments are identified that can induce [PSI +] appearance but can't maintain [PSI +].; Two types of mutations that cause nonsense suppression are identified in SUP35 or SUP45. The first type is a missense mutation which creates a nonsense suppression phenotype that becomes hidden during growth in the presence of millimolar guanidine. The second type is a nonsense mutation that is not affected by guanidine. These phenomena are independent of HSP104.