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Extracellular Small RNAs in Human Milk: Molecular Profiles, Stability and Fragment-Specific Responses in Cell-Based
Clara Claus1,2, Carla Borini Etichetti2, Bruno Costa3,4
1Institute of Clinical and Experimental Immunology of Rosario, Suipacha 590, Rosario 2000, Argentina.
Non-Coding RNA
|February 20, 2026
Summary
Human milk contains abundant, stable small RNA fragments from tRNA, yRNA, and rRNA. These milk-derived extracellular RNAs show potential to influence cellular stress responses in vitro.
Area of Science:
- Molecular Biology
- Human Milk Composition
- Extracellular RNA Biology
Background:
- Human milk is a complex fluid containing bioactive molecules, including extracellular RNAs (exRNAs).
- Abundant small RNA families like tRNA-, yRNA-, and rRNA-derived fragments in milk are underexplored.
- Detailed characterization of these abundant milk exRNAs is needed.
Purpose of the Study:
- To define the composition, fragmentation patterns, stability, and functional activity of abundant small RNAs in human milk.
- To compare milk RNA profiles with other biofluids.
- To investigate the subcellular distribution and potential cellular effects of milk exRNAs.
Main Methods:
- Small RNA sequencing of skim milk samples.
- RNA stability assays, Northern blotting, and RT-qPCR.
- Analysis of extracellular vesicle (EV) and non-vesicular fractions.
- In vitro functional assays using synthetic RNA fragments.
Main Results:
- Human milk is enriched in stable, abundant small RNA fragments from tRNA, yRNA, and rRNA.
- Milk RNA profiles are reproducible and distinct from other biofluids, with levels exceeding serum by >100-fold.
- Full-length transcripts are mainly in EVs, while shorter fragments are in the non-vesicular fraction.
- Synthetic milk exRNAs demonstrated pro-survival activity in vitro under stress.
Conclusions:
- Human milk harbors a distinct set of highly abundant, stable small RNAs derived from tRNA, yRNA, and rRNA.
- These findings enhance understanding of milk's RNA cargo.
- Preliminary evidence suggests milk-derived sRNA fragments can modulate cellular stress responses in vitro.
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