LUTI-dependent Downregulation of a Cell Cycle Transcription Factor is Key for Timely Meiotic Entry
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae SK1
PROVIDER: GSE225963 | GEO | 2023/12/05
REPOSITORIES: GEO
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Project description:Commitment to cell division at the end of G1 phase, termed Start in the budding yeast Saccharomyces cerevisiae, is strongly influenced by nutrient availability. To identify new dominant activators of Start that might operate under different nutrient conditions, we screened a genome-wide ORF overexpression library for genes that bypass a Start arrest caused by absence of the G1 cyclin Cln3 and the transcriptional activator Bck2. We recovered a hypothetical gene YLR053c, renamed NRS1 for Nitrogen-Responsive Start regulator 1, which encodes a poorly characterized 108 amino acid microprotein. Endogenous Nrs1 was nuclear-localized, restricted to poor nitrogen conditions, induced upon mTORC1 inhibition, and cell cycle-regulated with a peak at Start. NRS1 interacted genetically with SWI4 and SWI6, which encode subunits of the main G1/S transcription factor complex SBF. Correspondingly, Nrs1 physically interacted with Swi4 and Swi6 and was localized to G1/S promoter DNA. Nrs1 exhibited inherent transactivation activity and fusion of Nrs1 to the SBF inhibitor Whi5 was sufficient to suppress other Start defects. Nrs1 appears to be a recently evolved microprotein that rewires the G1/S transcriptional machinery under poor nutrient conditions.
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Project description:Candida albicans is an opportunistic pathogenic fungus that is able to assume several morphologies, including yeast and hyphal growth forms. The hyphal morphology can be induced by various environmental stimuli and is accompanied by expression of a large set of hyphal-specific genes (HSGs). Cell cycle and morphogenetic programs are interconnected: notably, inhibition of cell cycle progression often causes a switch to filamentous growth. Here we identify and characterize CaNrm1, a C. albicans homolog of the S. cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription program in the G1 phase and at the G1/S transition. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. Deletion of CaNRM1 causes a reduction in cell size and results in increased resistance to hydroxyurea (HU), an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of HU, suggests that its transcriptional induction in response to HU is mainly dependent upon CaNrm1. Genetic epistasis analysis suggests that CaNrm1 interacts with the SBF and MBF transcription factors in S. cerevisiae and with the MBF functional homolog in C. albicans. At the transcription level, deletion of CaNRM1 causes an induction of many G1 and G1/S-specific genes. Induction of the HSGs is dampened under certain conditions in the Canrm1-/- mutant, suggesting that the cell cycle transcription program influences the morphogenetic transcription program of C. albicans. One aspect of the characterization of the C. albicans Whi5/Nrm1 gene was to examine how this molecule influences global gene expression. To that end, we isolated total RNA from log-phase nrm1-/nrm1- (as well as parent/background strain) cells in two independent replicate experiments. These samples were processed, labeled, and subsequently used for hybridization of custom C. albicans Affymetrix arrays.
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Project description:Candida albicans is an opportunistic pathogenic fungus that is able to assume several morphologies, including yeast and hyphal growth forms. The hyphal morphology can be induced by various environmental stimuli and is accompanied by expression of a large set of hyphal-specific genes (HSGs). Cell cycle and morphogenetic programs are interconnected: notably, inhibition of cell cycle progression often causes a switch to filamentous growth. Here we identify and characterize CaNrm1, a C. albicans homolog of the S. cerevisiae Whi5 and Nrm1 transcription inhibitors that, analogous to mammalian Rb, regulate the cell cycle transcription program in the G1 phase and at the G1/S transition. CaNRM1 is able to complement the phenotypes of both whi5 and nrm1 mutants in S. cerevisiae. Deletion of CaNRM1 causes a reduction in cell size and results in increased resistance to hydroxyurea (HU), an inhibitor of DNA replication; analysis of the expression of ribonucleotide reductase, the target of HU, suggests that its transcriptional induction in response to HU is mainly dependent upon CaNrm1. Genetic epistasis analysis suggests that CaNrm1 interacts with the SBF and MBF transcription factors in S. cerevisiae and with the MBF functional homolog in C. albicans. At the transcription level, deletion of CaNRM1 causes an induction of many G1 and G1/S-specific genes. Induction of the HSGs is dampened under certain conditions in the Canrm1-/- mutant, suggesting that the cell cycle transcription program influences the morphogenetic transcription program of C. albicans.
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