Biology subjects

Tallada, V. A.

Publications and source records attributed to Tallada, V. A..

3 recordsLinked to original sources

bioRxiv2024

A key role of the EMC complex for mitochondrial respiration and quiescence in fission yeasts

In eukaryotes, oxygen consumption is mainly driven by the respiratory activity of mitochondria, which generates most of the cellular energy that sustains life. This parameter provides direct information about mitochondrial activity of all aerobic biological systems. Using the Seahorse analyzer instrument, we show here that deletion of the oca3/emc2 gene (oca3{Delta}) encoding the Emc2 subunit of the ER membrane complex (EMC), a conserved chaperone/insertase which aids membrane protein biogenesis in the ER, severely affects oxygen consumption rates and quiescence survival in Schizosaccharomyces pombe yeast cells. Remarkably, the respiratory defects of the oca3{Delta} mutation (EMC dysfunction) is rescued synergistically by the disruption of ergosterol biosynthesis (erg5{Delta}) and the action of the membrane fluidizing agent tween 20, suggesting a direct role of membrane fluidity and sterols composition in mitochondrial respiration in the fission yeast.

cell biology↗

bioRxiv2019

Physiological changes during cellular ageing in fission yeast drive non-random patterns of genome rearrangements

Aberrant repair of DNA double-strand breaks can recombine distant pairs of chromosomal breakpoints. Such chromosomal rearrangements are a hallmark of ageing and compromise the structure and function of genomes. Rearrangements are challenging to detect in non-dividing cell populations, because they reflect individually rare, heterogeneous events. The genomic distribution of de novo rearrangements in non-dividing cells, and their dynamics during ageing, remain therefore poorly characterized. Studies of genomic instability during ageing have focussed on mitochondrial DNA, small genetic variants, or proliferating cells. To gain a better understanding of genome rearrangements during cellular ageing, we focused on a single diagnostic measure - DNA breakpoint junctions - allowing us to interrogate the changing genomic landscape in non-dividing cells of fission yeast (Schizosaccharomyces pombe). Aberrant DNA junctions that accumulated with age were associated with microhomology sequences and R-loops. Global hotspots for age-associated breakpoint formation were evident near telomeric genes and linked to remote breakpoints on the same or different chromosomes, including the mitochondrial chromosome. An unexpected mechanism of genomic instability caused more local hotspots: age-associated reduction in an RNA-binding protein could trigger R-loop formation at target loci. This finding suggests that biological processes other than transcription or replication can drive genome rearrangements. Notably, we detected similar signatures of genome rearrangements that accumulated in old brain cells of humans. These findings provide insights into the unique patterns and potential mechanisms of genome rearrangements in non-dividing cells, which can be triggered by ageing-related changes in gene-regulatory proteins.

genomics↗

bioRxiv2018

Fitness Landscape of the Fission Yeast Genome

BackgroundNon-protein-coding regions of eukaryotic genomes remain poorly understood. Diversity studies, comparative genomics and biochemical outputs of genomic sites can be indicators of functional elements, but none produce fine-scale genome-wide descriptions of all functional elements.\n\nResultsTowards the generation of a comprehensive description of functional elements in the haploid Schizosaccharomyces pombe genome, we generated transposon mutagenesis libraries to a density of one insertion per 13 nucleotides of the genome. We applied a five-state hidden Markov model (HMM) to characterise insertion-depleted regions at nucleotide-level resolution. HMM-defined functional constraint was consistent with genetic diversity, comparative genomics, gene-expression data and genome annotation.\n\nConclusionsWe infer that transposon insertions lead to fitness consequences in 90% of the genome, including 80% of the non-protein-coding regions, reflecting the presence of numerous non-coding elements in this compact genome that have functional roles. Display of this data in genome browsers provides fine-scale views of structure-function relationships within specific genes.

genomics↗