Lack of Pseudouridine Synthase 7 Enzyme Sensitizes Yeast Cells to DNA-Damaging Agents

RNA modifications are essential in reshaping the chemistry of RNA molecules, influencing their structure, function, and stability. Up to now, more than 160 different types of modifications have been discovered among different RNA species. One prominent modification is the enzymatic transformation of uridine (U) into pseudouridine (Ψ), a process facilitated by pseudouridine synthase (Pus) enzymes, which occurs in both coding (mRNA) and non-coding (ncRNA) RNA species. Among the enzymes responsible for this transformation, Pus7 stands out due to its association with certain developmental and physical conditions. Research links Pus7 to intellectual disabilities, delayed speech development, microcephaly, and short stature. Despite its association with these disorders, the exact biological role and mechanism of Pus7 remain poorly understood, leaving room for further investigation. In this study, we aimed to understand the role of Pus7 in Saccharomyces cerevisiae cells under DNA damage stress. To achieve this, wild-type and pus7Δ cells were subjected to varying concentrations of DNA-damaging agents, including ultraviolet (UV) light and the chemical methyl methanesulfonate (MMS). Survival curves and spot plating assay results demonstrated that pus7Δ cells exhibit growth defects when exposed to 2 mM MMS or 15 J/m² UV light. These findings indicate that the absence of Pus7 enzyme renders yeast cells sensitive to DNA-damaging agents. Further research is necessary to investigate the role of Pus7 under DNA damage stress, which contributes to genomic instability - a hallmark of many cancers.