Comparative Transcriptomic Analyses Reveal Potential Stp1 Regulatory Roles Independent of Sre1 in Phaffia rhodozyma

Sterol regulatory element-binding proteins (SREBPs) regulate lipid homeostasis in mammals via sequential activation by the site-1 (S1P) and site-2 (S2P) proteases. In the yeast <i>Phaffia rhodozyma</i>, homologs of SREBP (Sre1) and S2P (Stp1) were identified, with Sre1 cleaved by Stp1 and involved in the regulation of sterol and carotenoid biosynthesis. Additional regulatory roles of S2P have been described in other organisms, but such functions remain unexplored in <i>P. rhodozyma</i>, a question addressed in this study. Transcriptomic analyses of Δ<i>sre1</i>, Δ<i>stp1</i>, and Δ<i>sre1</i>Δ<i>stp1</i> mutants were performed in both wild-type and Sre1-activated conditions. Potential genes regulated by Stp1 independently of Sre1 were identified, and their cellular roles were determined by KEGG mapping and Gene Ontology classification. As expected, most transcriptional changes in Δ<i>stp1</i> mutants reflected Sre1-mediated regulation. Notably, a subset of genes displayed differential expression independently of Sre1. These genes were linked to diverse aspects of cellular homeostasis, including metabolism, protein folding, ER stress response, and ribosome biogenesis. The transcriptomic analysis suggests that Stp1 regulates gene expression beyond the Sre1 transcription factor in <i>P. rhodozyma</i>, providing a framework for future studies to confirm and further explore these functions.