Functional Annotation of Uncharacterised Proteins Whose Expression Patterns Affect the Lifespan under Metformin Treatment in Fission Yeast


Tarhan Ç., Çalıcı Z., Özden B.

European Journal of Biology, vol.82, no.2, pp.196-211, 2023 (Scopus) identifier

Abstract

Objective: Metformin, a well-known anti-diabetic drug and a caloric restriction mimetic, seems to attenuate aging through myriad cellular processes, wherein most of its mode of action is still elusive. Thus, bioinformatic analyses that might direct experimental studies are crucial. Moreover, uncharacterised proteins with unknown molecular functions might withhold information regarding metformin’s mode of action. Here, we aimed to elucidate genes encoding uncharacterised proteins that are somehow involved in metformin metabolism and elaborate their involvement through functional annotation to reveal novel cellular processes in which metformin interferes.

Materials and Methods: Total RNA isolation was conducted from Schizosaccharomyces pombe wild-type cells that were grown in standard and overnutrition conditions. Following the gene expression analysis of the uncharacterised proteins, the bioinformatics analysis of the up- and down-regulated uncharacterised proteins upon metformin treatment in both was conducted using the functional annotator called PANNZER2.

Results: Genes that might be related to cellular processes such as meiosis, protein folding, calcium homeostasis, and heme production are up- and down-regulated upon metformin treatment. Moreover, the up-regulation of apoptosis and antioxidationrelated genes and the down-regulation of mitosis, DNA damage, apoptosis, mitochondria, and telomere-capping-related genes were also determined.

Conclusion: We effectively identified associations between metformin and a wide range of cellular processes and genetic mechanisms through the comprehensive annotation of uncharacterised genes. Our findings are consistent with the literature, and many of these uncharacterised proteins could be used as targets for research into aging in the future.