Research, Research Articles
Fungal stress responses from the view of transcriptome vectors
Károly Antal1, István Pócsi2,3 and Tamás Emri2,3,*
The paper introduces a spatial model of transcriptomes, where stress responses are vectors. It explains why comparisons are difficult and how this approach improves interpretation.
Scp160 deletion suppresses TDP-43 aggregation and toxicity in Saccharomyces cerevisiae
Joan Castells-Ballester and Natalia Shcherbik
Deletion of SCP160 or BFR1 reduces TDP-43 toxicity without lowering TDP-43 protein abundance and suppresses prominent TDP-43, Htt103Q, and VHL aggregation, while SCP160 deletion also shifts residual TDP-43 foci toward the ER.
The p53 DNA-Binding (Core) Domain can form a prion that seeds prion formation in full-length p53
Mathilde Kadouch1, Christelle Marchal1, Sei-Kyoung Park2, Sangeun Park2, Sabine Castano1, Susan W. Liebman2 and Christophe Cullin1
In yeast the p53 core-domain forms a self-propagating prion that inactivates a reporter and converts untagged full-length p53 to a prion. R175H in the tagged chimera shows 18x higher prionization, linking it to p53 inactivation in human cancers.
Sorbic acid triggers rapid formation of proteasome storage granules in Saccharomyces cerevisiae
Shoei Tanaka1, Mitsuki Imajo1, Mieko Hayashi2, Akira Matsuura2 and Shingo Izawa1
This study demonstrates that sorbic acid, a common food preservative, induces the fastest reported proteasome storage granule (PSG) formation in yeast within 30 min, highlighting differences from other PSG-inducing conditions like acetic acid stress.
A time-resolved high-throughput screening of fission yeast deletion mutants for oxidative stress resistance
Mohammadtaha Pirsalehi, Rowshan Ara Islam, Kristal Ng, Olga Xintarakou, Peter Harold Thorpe and Charalampos Rallis
By capturing dynamic trajectories rather than static outcomes, this study exposes hidden layers of growth under oxidative stress and identifies new genetic determinants of cellular resilience in fission yeast.
Clonal spread and environmental persistence of carbapenem-resistant high-risk Pseudomonas aeruginosa in critical-care units of a Chilean national referral center for burn and trauma patients (2022)
Camila Ibarra1, Gustavo Araya2, Alhejandra Alvarez2, Leonardo Enríquez2, Carolina Arellano2, Fabricio Alarcón1, Constanza Fernández1, Claudio Vargas1, Rodrigo Vera1 and Roberto M. Vidal2
This study highlight the circulation of high-risk P. aeruginosa clones in Chile and underscore the importance of molecular epidemiology in guiding infection control, optimizing antimicrobial therapy, and mitigating the clinical and economic burden of CRPA.
The transcriptome of dendritic cells redraws the boundaries between pathogenicity and commensalism in yeast
Lisa Rizzetto1, Irene Stefanini2, Stefano Nenciarini3, Monica Di Paola3, Samantha Riccadonna1, Ivo G. Gut4,5, Marta Gut4,5, Simon Heath4,5 and Duccio Cavalieri3
Our immune system meets many fungi, but reacts strongly to only a few. The comparison of key fungal species showed that responses differ mainly in timing and not just genes, highlighting the need to rethink what makes fungi harmful vs. harmless.
Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae
Çağla Ece Olgun1,a, Gizem Turan Duman1,a, Gizem Güpür1, Hamit İzgi1, Mariam Huda2, Demet Çetin3, Zekiye Suludere4, Fatma Küçük Baloğlu5, Ayşe Koca Çaydaşı2 and Mesut Muyan1
This study demonstrates that the conserved yeast protein Moh1 links metabolism, gene expression, and cell structure, thereby altering cell envelope permeability and leading to selective stress responses.
Fungistatic effect of sorbic acid on yeast cells via translational repression involving eIF2α phosphorylation and formation of Ded1- and eIF2B-granules
Haruka Yoshiyama1, Wataru Nomura2 and Shingo Izawa1
The findings of this study provide new insights into the physiological effects of sorbic acid on yeast cells, specifically regarding the regulation of translation-related factors.
Ergosterone-coupled Triazol molecules trigger mitochondrial dysfunction, oxidative stress, and acidocalcisomal Ca2+ release in Leishmania mexicana promastigotes
December 11, 2015
The protozoan parasite Leishmania causes a variety of sicknesses with different clinical manifestations known as leishmaniasis. Investigations looking for new targets or new active molecules focus mainly on the disruption of parasite specific pathways. In this sense, ergosterol biosynthesis is one of the most attractive because it does not occur in mammals. Our results indicate that ergosterone-triazol coupled molecules induce a regulated cell death process in the parasite and may represent starting point molecules in the search of new chemotherapeutic agents to combat leishmaniasis.
INO1 transcriptional memory leads to DNA zip code-dependent interchromosomal clustering
November 13, 2015
Many genes localize at the nuclear periphery through physical interaction with the nuclear pore complex (NPC). We have found that the yeast INO1 gene is targeted to the NPC both upon activation and for several generations after repression, a phenomenon called epigenetic transcriptional memory. Targeting of INO1 to the NPC requires distinct cis-acting promoter DNA zip codes under activating conditions and under memory conditions. When at the nuclear periphery, active INO1 clusters with itself and with other genes that share the GRS I zip code. Here, we show that during memory, the two alleles of INO1 cluster in diploids and endogenous INO1 clusters with an ectopic INO1 in haploids. After repression, INO1 does not cluster with GRS I - containing genes. Furthermore, clustering during memory requires Nup100 and two sets of DNA zip codes...
A central role for TOR signalling in a yeast model for juvenile CLN3 disease
November 11, 2015
Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. Bond et al. study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe.
Oxygen availability strongly affects chronological lifespan and thermotolerance in batch cultures of Saccharomyces cerevisiae
October 22, 2015
Stationary-phase (SP) batch cultures of Saccharomyces cerevisiae, in which growth has been arrested by carbon-source depletion, are widely applied to study chronological lifespan, quiescence and SP-associated robustness. Based on this type of experiments, typically performed under aerobic conditions, several roles of oxygen in aging have been proposed. However, SP in anaerobic yeast cultures has not been investigated in detail. Here, we use the unique capability of S. cerevisiae to grow in the complete absence of oxygen to directly compare SP in aerobic and anaerobic bioreactor cultures. This comparison revealed strong positive effects of oxygen availability on adenylate energy charge, longevity and thermotolerance during SP. A low thermotolerance of...
DNA damage checkpoint adaptation genes are required for division of cells harbouring eroded telomeres
September 21, 2015
In budding yeast, telomerase and the Cdc13p protein are two key players acting to ensure telomere stability. This article shows that while the capping process can be flexible, it takes a very specific genetic setup to allow a change from canonical capping to alternative capping.
The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway
September 6, 2015
Oxidative stress stimulates the Rho1 GTPase, which in turn induces the cell wall integrity (CWI) MAP kinase cascade. CWI activation promotes stress-responsive gene expression through activation of transcription factors (Rlm1, SBF) and nuclear release and subsequent destruction of the repressor cyclin C. This study reports that, in response to high hydrogen peroxide exposure, or in the presence of constitutively active Rho1, cyclin C still translocates to the cytoplasm and is degraded in cells lacking Bck1, the MAPKKK of the CWI pathway.
Formyl-methionine as a degradation signal at the N-termini of bacterial proteins
September 6, 2015
Varshavsky and colleagues solve a long-standing mystery in proteolysis! In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N‑terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in...
A single mutation in the 15S rRNA gene confers non sense suppressor activity and interacts with mRF1 the release factor in yeast mitochondria
August 2, 2015
This article presents the nucleotide sequence of the mim3-1 mitochondrial ribosomal suppressor, acting on ochre mitochondrial mutations and one frameshift mutation in Saccharomyces cerevisiae. A hypothetical mechanism of suppression by "ribosome shifting" is also discussed in view of the nature of mutations suppressed and not suppressed.
The lysosomotropic drug LeuLeu-OMe induces lysosome disruption and autophagy-independent cell death in Trypanosoma brucei
July 30, 2015
Trypanosoma brucei is a blood-borne, protozoan parasite that causes African sleeping sickness in humans and nagana in animals. The current chemotherapy relies on only a handful of drugs that display undesirable toxicity, poor efficacy and drug-resistance. In this study, we explored the use of lysosomotropic drugs to induce bloodstream form T. brucei cell death via lysosome destabilization. We measured drug concentrations that inhibit cell proliferation by 50% (IC50) for several compounds, chosen based on their lysosomotropic effects previously reported in Plasmodium falciparum. The lysosomal effects and cell death induced by L-leucyl-L-leucyl methyl ester (LeuLeu-OMe) were further analyzed by flow cytometry and immunofluorescence analyses of different lysosomal markers...