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The 5-Fluorouracil RNA Expression Viewer (5-FU) Facilitates Interpreting the Effects of Drug Treatment and RRP6 Deletion on the Transcriptional Landscape in Yeast.
Yeast
October 2024
Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Rennes, France.
Saccharomyces cerevisiae is an excellent model to study the effect of external cues on cell division and stress response. 5-Fluorocuracil (5-FU) has been used to treat solid tumors since several decades. The drug was initially designed to interfere with DNA replication but was later found to exert its antiproliferative effect also via RNA-dependent processes.
View Article and Find Full Text PDFEvidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation.
Biochem J
April 2024
School of Natural Sciences, Massey University, Auckland, New Zealand.
The protein kinase Gcn2 and its effector protein Gcn1 are part of the general amino acid control signalling (GAAC) pathway best known in yeast for its function in maintaining amino acid homeostasis. Under amino acid limitation, Gcn2 becomes activated, subsequently increasing the levels of phosphorylated eIF2α (eIF2α-P). This leads to the increased translation of transcriptional regulators, such as Gcn4 in yeast and ATF4 in mammals, and subsequent re-programming of the cell's gene transcription profile, thereby allowing cells to cope with starvation.
View Article and Find Full Text PDFXRN1 deletion induces PKR-dependent cell lethality in interferon-activated cancer cells.
Cell Rep
February 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
Emerging data suggest that induction of viral mimicry responses through activation of double-stranded RNA (dsRNA) sensors in cancer cells is a promising therapeutic strategy. One approach to induce viral mimicry is to target molecular regulators of dsRNA sensing pathways. Here, we show that the exoribonuclease XRN1 is a negative regulator of the dsRNA sensor protein kinase R (PKR) in cancer cells with high interferon-stimulated gene expression.
View Article and Find Full Text PDFeIF2A represses cell wall biogenesis gene expression in Saccharomyces cerevisiae.
PLoS One
November 2023
Institut Pasteur, Génétique des Interactions Macromoléculaires, Centre National de la Recherche Scientifique, UMR 3525, Paris, France.
Translation initiation is a complex and highly regulated process that represents an important mechanism, controlling gene expression. eIF2A was proposed as an alternative initiation factor, however, its role and biological targets remain to be discovered. To further gain insight into the function of eIF2A in Saccharomyces cerevisiae, we identified mRNAs associated with the eIF2A complex and showed that 24% of the most enriched mRNAs encode proteins related to cell wall biogenesis and maintenance.
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