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Determine the cellular origins and physiological functions of extracellular microRNAs

Determine the cellular origins and specific physiological functions of extracellular microRNAs present in biological fluids, identifying the contributing tissues and cell types and elucidating their roles in recipient cells.

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Background

The paper discusses that microRNAs are detected stably across diverse biological fluids and are carried by multiple transport modalities, including ribonucleoprotein complexes (e.g., AGO2-associated), extracellular vesicles (exosomes and microvesicles), and lipoproteins (HDL and LDL). Despite this extensive detection and carrier diversity, the authors emphasize that the field faces significant methodological challenges that impede tracing the sources and functions of these extracellular microRNAs.

Within the broader hypothesis of specialized ncRNA-secreting cellular organizations (“NAcrins”), clarifying which tissues and cell types release extracellular microRNAs, and what biological roles these molecules perform once delivered to recipient cells, is crucial to understanding intercellular regulation and potential systemic homeostatic mechanisms mediated by ncRNAs.

References

And it is all the more intriguing when we come down to the idea that we do not know the origin and functions of these extracellular miRNAs, a consequence that can be attributed to the numerous and complex methodological challenges.

— Stumbling around uncharted regulatory structures: NAcrins, or the perspective of specialized sources of modulatory non-coding RNAs (2506.17322 - Benzaki, 18 Jun 2025) in Section “Carriers, stoichiometry and transfer”