Mechanisms of recipient-cell uptake of extracellular microRNAs

Investigate and define the cellular mechanisms by which recipient cells internalize extracellular microRNAs, distinguishing among macropinocytosis, clathrin-mediated endocytosis, scavenger receptor class B type 1 (SR-B1)-mediated uptake of HDL-bound microRNAs, direct membrane fusion, and gap junction transfer.

Background

Although several routes of uptake have been proposed for extracellular microRNAs—including endocytosis for exosomes and SR-B1-mediated uptake for HDL-bound microRNAs—the field lacks comprehensive in vivo validation and mechanistic delineation across cell types.

Clarifying uptake mechanisms will enable accurate modeling of intercellular RNA signaling and guide therapeutic delivery strategies.

References

To the best of our knowledge, absorption at the level of target cells remains poorly studied and based on hypothetical views.

Stumbling around uncharted regulatory structures: NAcrins, or the perspective of specialized sources of modulatory non-coding RNAs (2506.17322 - Benzaki, 18 Jun 2025) in Recipient cells, targets and tissue distribution