Beyond miRNAs: Molecular identity, mechanistic evidence, and cross-kingdom potential of rRNA- and tRNA-derived small RNAs in food-derived extracellular vesicles.

Authors

Xinping Chen, Mohan Li, Jiahui Zhang, Dianjiang Wang, Yan Zheng, Xiqing Yue

Published in

Food research international (Ottawa, Ont.). Volume 245. Issue Pt 4. Pages 120921. Dec 01, 2026. Epub Sep 28, 2026.

Abstract

Small RNAs derived from rRNAs and tRNAs (rsRNAs and tsRNAs) recur in preparations enriched for food-derived extracellular vesicles (EVs) and related nanoparticles, yet their biological significance remains uncertain. Once dismissed as degradation products, some now stand out because they recur at defined cleavage sites, persist extracellularly, or show regulatory activity. The evidence, however, is not equally mature for the two classes. tsRNAs have an established origin-based nomenclature, several experimentally supported biogenesis pathways, and diverse mechanisms of action. Most rsRNA studies still identify recurrent sequencing hotspots or a few candidate fragments, with limited evidence for regulated production or direct function. Here, we place rsRNAs and tsRNAs in direct comparison across molecular identity, biogenesis, analytical recovery, extracellular partitioning, target recognition, regulatory mechanisms, and biological outcomes. Evidence from animal-derived foods, edible plants, and food-associated microorganisms shows that detection in a particle-associated preparation is frequently conflated with intraparticle localization, delivery, or causality. Although selected milk- and microbe-associated tsRNAs have been linked to defined targets or recipient responses, food-associated rsRNA evidence remains largely descriptive. Neither class has yet been followed from an exact endogenous fragment in its native carrier through physiologically relevant delivery to fragment-dependent function. To make these distinctions explicit, we propose the fragment identity-carrier context-recipient response (F-C-R) framework as a practical evidence-assessment tool, not a universal biological mechanism. It organizes what has been demonstrated, identifies what remains inferred, and defines the experiments needed to establish native-carrier causality.

PMID:
42967733
Bibliographic data and abstract were imported from PubMed on 02 Nov 2026.

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