Transcriptomic analysis of Rnq1 loss and prionization reveals alterations in translation pathways and energy metabolism.

Prion proteins can undergo self-perpetuating conformational changes that alter their functions. One such protein, Rnq1, whose prion form acts as a master regulator of several other prions’ formation and transmission, is unknown for its physiological functions. Here, we investigated how Rnq1 loss and prionization affect the yeast transcriptomic profile. We found that both the Rnq1 loss and prionization exert similar global effects on the transcriptome, with more transcripts upregulated than downregulated. Notably, the upregulated differentially expressed genes (DEGs) were predominantly enriched for translation-related gene ontology (GO) terms, largely due to the overrepresentation of snoRNAs and tRNAs. In contrast, the downregulated DEGs were primarily associated with energy production, especially in mitochondria. Interestingly, the Rnq1 prion mainly exhibited amplified loss-of-function effects. Further analyses suggest that, as a low-complexity protein, Rnq1 has evolved to interact with multiple cellular partners to maintain physiological balance, particularly between protein synthesis and energy production. The loss and prionization of Rnq1 may disrupt these natural interactions, thereby triggering feedback regulations and/or perturbing RNA processing through crosstalk among transcription factors, RNA polymerases, and other cellular machinery. Together, our results provide new insights into Rnq1 functions and prion-mediated cellular behaviors with broader implications of prion-based phenomena across biological systems.