Microbiology Research, Vol. 15, Pages 508-524: Transcription Factors Mcm1 and Sfp1 May Affect [PSI+] Prion Phenotype by Altering the Expression of the SUP35 Gene

Microbiology Research, Vol. 15, Pages 508-524: Transcription Factors Mcm1 and Sfp1 May Affect [PSI+] Prion Phenotype by Altering the Expression of the SUP35 Gene

Microbiology Research doi: 10.3390/microbiolres15020034

Authors: Andrew G. Matveenko Anastasiia S. Mikhailichenko Polina B. Drozdova Galina A. Zhouravleva

Mcm1 is an essential Q/N-rich transcription factor. Q/N-rich proteins interact with each other, and many affect the [PSI+] prion formed by the translation termination factor Sup35 (eRF3). We found that transient MCM1 overexpression increased nonsense suppression in [PSI+] strains and SUP35 transcription. As we had discovered similar effects of another Q/N-rich transcription factor, Sfp1, here we focus on the roles of Mcm1 and Sfp1 in SUP35 expression, as well as on the effects of Sfp1 on the expression of the gene encoding another release factor, Sup45 (eRF1). Mutations in the SUP35 promoter showed that none of the potential Mcm1 binding sites affected the Sup35 protein level or nonsense suppression, even during MCM1 overexpression. Mcm1 itself neither formed aggregates in vivo nor affected Sup35 aggregation. In contrast, a mutation in the Sfp1-binding site decreased Sup35 production and [PSI+] toxicity of excess Sfp1. Mutation of the Sfp1 binding site in the SUP45 promoter lowered SUP45 expression and increased nonsense suppression even more drastically. Our data indicate that the mechanisms of Mcm1 and Sfp1 action differ. While Mcm1 seems unlikely to directly regulate SUP35 expression, Sfp1 appears to act through its binding sites and to directly activate SUP35 expression, which in turn may influence the [PSI+] prion phenotype and toxicity.