Yeast Eats RNA Oligonucleotides as Excellent Nitrogen Source Via Endocytosis, Autophagy, and RNA Degradation

Nucleic acids are significant components of daily diet and have attracted attention regarding their metabolic and nutritional roles. Numerous studies have explored the biological functions of nucleotides, nucleosides, and functional nucleic acids like microRNAs. However, the nutritional value and metabolic mechanisms of RNA oligonucleotides derived from ribosomal RNA (rRNA)—a major form of nucleic acids in nature remain underexplored. Here, yeast was utilized as a model organism to investigate the absorption and metabolism of oligonucleotides obtained from rRNA. We cultured yeast directly using RNA oligonucleotides as one nutrient, demonstrating that yeast can efficiently utilize RNA oligonucleotides (length < 30 nt) as a nitrogen source. Through proteomic analysis to assess the expression levels of key proteins associated with transport and metabolic processes, we found that the key proteins involved in endocytosis, autophagy, and RNA degradation were upregulated. These results clearly demonstrate that yeast directly uptakes RNA oligonucleotides via endocytosis, which are subsequently degraded into nucleosides, ammonia and β-Alanine through autophagy and RNA degradation, thus providing substrates for synthesizing nucleic acid and other organic nitrogenous metabolites. Our findings and proposed mechanisms for RNA absorption and metabolism in eukaryotic cells can promote future research in both nutrition and nucleic acid metabolism.