Mutations of PRS1 and PRS5 impair Saccharomyces cerevisiae response to cell wall integrity and rapamycin treatment

Paraskevi-Ioanna Linardou, Mikolaj Patyna, Lilian Mary Schweizer, Robbie Loewith, Michael Schweizer

Research output: Contribution to conferenceAbstract

Abstract

The Saccharomyces cerevisiae genome contains five PRS genes (PRS1-PRS5). Theoretically, each of the Prs polypeptides is capable of synthesizing phosphoribosyl pyrophosphate (PRPP), required for the synthesis of purine and pyrimidine nucleotides and histidine and tryptophan, but yeast can only survive if one of the following functional entities–Prs1/Prs3, Prs2/Prs5 or Prs4/Prs5–is present. Prs1 and Prs5 differ in length from Prs2, Prs3 and Prs4 since they contain non-homologous regions, designated NHR1-1, NHR5-1 and NHR5-2, respectively. Deletion of NHR1-1 causes a significant increase in PRPP synthetase activity and prevents the interaction with Slt2, allowing enzyme activity and maintenance of CWI to be separated.

Rapamycin inhibits TORC1 resulting in the activation of the cell wall integrity (CWI) pathway (Loewith&Hall, 2011). Phosphoproteome analyses indicated that Prs5 is phosphorylated upon rapamycin treatment (Huber et al., 2009), which we have now confirmed through gel-shift assays. Multiple alanine substitutions of the three phosphosites S364, S367 and S369 in NHR5-2 compromise Rlm1 expression upon rapamycin treatment.

It appears that the PRS gene family has, as result of gene duplication and acquisition of NHRs, evolved to link two essential functions, PRPP synthesis and CWI, to regulation by TORC1.
Original languageEnglish
Publication statusPublished - 22 Aug 2023
Event31st International Conference on Yeast Genetics and Molecular Biology 2023 - Florence, Italy
Duration: 20 Aug 202325 Aug 2023

Conference

Conference31st International Conference on Yeast Genetics and Molecular Biology 2023
Abbreviated titleICYGMB31
Country/TerritoryItaly
CityFlorence
Period20/08/2325/08/23

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