Showing papers by "Jürg Bähler published in 2022"
TL;DR: In this paper , the authors compare two related fission yeast, Schizosaccharomyces pombe and S. japonicus, as a comparative model system, highlighting the versatility and plasticity of central carbon metabolism in eukaryotes, illuminating critical adaptations supporting the preferential use of glycolysis over oxidative phosphorylation.
3 citations
TL;DR: It is proposed that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis.
Abstract: Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regulating transcription. Interestingly, it is becoming apparent that the metabolic state of the cell and certain metabolites can directly control the epigenetic information and gene expression. In the fission yeast Schizosaccharomyces pombe, the conserved Sty1 stress-activated protein kinase cascade is the main pathway responding to most types of stresses, and regulates the transcription of hundreds of genes via the Atf1 transcription factor. Here we report that fission yeast cells defective in fatty acid synthesis (cbf11, mga2 and ACC/cut6 mutants) show increased expression of a subset of stress-response genes. This altered gene expression depends on Sty1, and the Gcn5 and Mst1 histone acetyltransferases, is associated with increased acetylation of histone H3 at lysine 9 in the corresponding gene promoters, and results in increased cellular resistance to oxidative stress. Since both fatty-acid synthesis and histone acetylation compete for the same substrate, acetyl-CoA, we propose that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis.
2 citations
TL;DR: In this paper , the authors show that genetic perturbations lead to molecular changes that are confined to small parts of a network versus when they lead to large-scale adaptations of global network states.
Abstract: The complexity of many cellular and organismal traits results from poorly understood mechanisms integrating genetic and environmental factors via molecular networks. Here, we show when and how genetic perturbations lead to molecular changes that are confined to small parts of a network versus when they lead to large-scale adaptations of global network states. Integrating multi-omics profiling of genetically heterogeneous budding and fission yeast strains with an array of cellular traits identified a central state transition of the yeast molecular network that is related to PKA and TOR (PT) signaling. Genetic variants affecting this PT state globally shifted the molecular network along a single-dimensional axis, thereby modulating processes including energy- and amino acid metabolism, transcription, translation, cell cycle control and cellular stress response. We propose that genetic effects can propagate through large parts of molecular networks because of the functional requirement to centrally coordinate the activity of fundamental cellular processes. Graphical abstract Graphical abstract: Genetic variants directly or indirectly affecting the activity of PKA and/or TOR signaling cause global changes of transcriptomic and proteomic network states by modulating the activity of diverse cellular functions and network modules. Using marker genes acting downstream of PKA and TOR signaling we are able to quantify the activity status of combined PKA and TOR signaling (‘PT Score’). This PT Score correlates with major transcriptomic and proteomic changes in response to genetic variability. Those large-scale molecular adaptations correlate with and explain phenotypic consequences for multiple cellular traits. Variants affecting the stoichiometry of proteins within a specific module have regional effects that remain confined to smaller parts of the molecular network. Variants affecting only one or very few proteins change molecular networks only locally. The global reorganization of network states caused by variants of the first type result in consequences for many cellular traits (i.e. pleiotropic effects), such as growth on different carbon sources, stress response, energy metabolism and replicative lifespan. (Created with BioRender.com)
TL;DR: This work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and demonstrates that it is possible to detect urdylation marks in RNA-seq data without the need for specific methodologies.
Abstract: Messenger RNA uridylation is pervasive and conserved among eukaryotes, but the consequences of this modification for mRNA fate are still under debate. Utilising a simple model organism to study uridylation may facilitate efforts to understand the cellular function of this process. Here we demonstrate that uridylation can be detected using simple bioinformatics approach. We utilise it to unravel widespread transcript uridylation in fission yeast and demonstrate the contribution of both Cid1 and Cid16, the only two annotated terminal uridyltransferases (TUT-ases) in this yeast. To detect uridylation in transcriptome data, we used a RNA-sequencing (RNA-seq) library preparation protocol involving initial linker ligation to fragmented RNA. We next explored the data to detect uridylation marks. Our analysis shows that uridylation in yeast is pervasive, similarly to the ones in multicellular organisms. Importantly, our results confirm the role of the cytoplasmic uridyltransferase Cid1 as the primary uridylation catalyst. However, we also observed an auxiliary role of the second uridyltransferase, Cid16. Thus both fission yeast uridyltransferases are involved in mRNA uridylation. Intriguingly, we found no physiological phenotype of the single and double deletion mutants of cid1 and cid16 and only limited impact of uridylation on steady-state mRNA levels. Our work establishes fission yeast as a potent model to study uridylation in a simple eukaryote, and we demonstrate that it is possible to detect uridylation marks in RNA-seq data without the need for specific methodologies.
DOI•
TL;DR: In this article , it was discovered that the wrong data were used for the left graph in Figure 4A, resulting in the left graphs of Figure 4 A and 4 C to show the same data.
Abstract: We discovered that the wrong data were used for the left graph in Figure 4A, resulting in the left graphs of Figure 4A and 4C to show the same data. This error has been corrected by replacing the plot in Figure 4A with the correct plot showing the data for lincRNA mutants. We have also improved the right graph of Figure 4C by cutting the X axis to better represent the data range. The article has been corrected accordingly, and these corrections do not in any way change our conclusions. The corrected Figure 4 is shown here: The originally published Figure 4 is shown below for reference: Additional information