# Yeast Efficiently Utilizes Ribosomal RNA-Derived Oligonucleotides as Bioavailable Nutrient Sources

## TL;DR

Yeast can efficiently absorb and use short RNA fragments from ribosomal RNA as nutrients, supporting growth through specific cellular pathways.

## Contribution

Demonstrates for the first time that rRNA-derived oligonucleotides serve as bioavailable nutrients for yeast.

## Key findings

- Yeast efficiently utilizes RNA oligonucleotides (5–30 nt) for robust cell growth.
- Confocal microscopy shows rapid uptake of labeled RNA oligonucleotides by yeast cells.
- Proteomic analysis reveals upregulation of endocytosis and autophagy proteins in response to RNA oligonucleotides.

## Abstract

Nucleic acids are essential dietary components with diverse physiological functions. Numerous studies have focused on the biological functions of nucleotides, nucleosides, and functional RNAs such as microRNAs. However, the nutritional value of ribosomal RNA (rRNA)-derived oligonucleotides, which are likely the predominant nucleic acid-derived components in foods, remains largely unexplored. Here, yeast was used as a food-associated eukaryotic model organism to investigate the uptake and utilization of rRNA-derived oligonucleotides. Yeast efficiently utilized short RNA oligonucleotides (approximately 5–30 nt) as nutrient sources, supporting robust cell growth. Confocal microscopy confirmed rapid uptake of Cy5-labeled RNA oligonucleotides by yeast cells. Proteomic analysis further revealed marked upregulation of proteins involved in endocytosis and autophagy in yeast cultured with RNA oligonucleotides. Collectively, these findings demonstrate that yeast can internalize and metabolize rRNA-derived oligonucleotides as efficient nutrient sources, likely through coordinated endocytic and autophagic pathways. This study highlights the nutritional potential of rRNA-derived oligonucleotides and provides a foundation for their future application in functional foods and fermentation systems.