The BUD31 Homologous Gene in Schizosaccharomyces pombe Is Evolutionarily Conserved and Can Be Linked to Cellular Processes Regulated by the TOR Pathway

TL;DR

This study explores the role of the BUD31 gene in fission yeast and links it to processes regulated by the TOR pathway, which is important in cancer and aging.

Contribution

The study reveals that the BUD31 homolog in fission yeast is functionally linked to the TOR pathway and is evolutionarily conserved.

Findings

Cells lacking the cwf14 gene show defects in cell size, division, stress response, and aging, all regulated by the TOR pathway.

Genes affected by cwf14 deletion are upregulated and often encode hydrolases and oxidoreductases involved in transport.

BUD31 orthologs are conserved across species, and the human gene can partially rescue mutant yeast cells.

Abstract

The human BUD31 gene has been associated with various processes including cancer. To better understand its function, we used genetic methods to study Schizosaccharomyces pombe cells lacking the BUD31 homologous gene (cwf14) and performed sequence analysis using bioinformatics methods. Mutant cells lacking the cwf14 gene showed cell size and division defects, altered stress response, rapamycin sensitivity, enhanced chronological aging, and increased sporulation tendency. These processes are known to be regulated by the TOR pathway. The cwf14-TOR link was also supported by further experiments. We demonstrated that most protein-coding genes affected by cwf14 deletion are upregulated, encode hydrolases, oxidoreductases, and are often involved in transport. GO enrichment drew our attention to genes related to nitrogen transport, while additional data pointed to a nutrient/nitrogen (N) sensing problem. Although Cwf14 protein is associated with spliceosome complex, most genes affected by the absence of cwf14 do not contain introns, suggesting that they are influenced indirectly by the cwf14 gene. In silico experiments have revealed that BUD31 orthologous genes are found from yeast to humans, are evolutionarily conserved with a high degree of sequence identity, conserved motifs, and structures. Since the human gene partially complemented the mutant phenotype of S. pombe cells, indicating functional homology, our data can help better understand pathological mechanisms observed in human cancer cells.

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