4.7 Review

Examining the evidence for extracellular RNA function in mammals

Journal

NATURE REVIEWS GENETICS
Volume 22, Issue 7, Pages 448-458

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41576-021-00346-8

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Funding

  1. [U19CA179513]
  2. [U01CA217882]
  3. [U42OD026647]

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This review article discusses the evidence for a biological role of RNA as a form of cell-cell communication in mammals, as well as proposed roles for extracellular RNAs in health and disease. Furthermore, it emphasizes the experimental rigor needed to definitively show that extracellular RNAs are functional in recipient cells in vivo.
The presence of RNAs in the extracellular milieu has sparked the hypothesis that RNA may play a role in mammalian cell-cell communication. As functional nucleic acids transfer from cell to cell in plants and nematodes, the idea that mammalian cells also transfer functional extracellular RNA (exRNA) is enticing. However, untangling the role of mammalian exRNAs poses considerable experimental challenges. This Review discusses the evidence for and against functional exRNAs in mammals and their proposed roles in health and disease, such as cancer and cardiovascular disease. We conclude with a discussion of the forward-looking prospects for studying the potential of mammalian exRNAs as mediators of cell-cell communication. The authors review the evidence for a biological role of RNA as a form of cell-cell communication in mammals as well as proposed roles for extracellular RNAs in health and disease. Moreover, this Review emphasizes and provides guidance on the experimental rigor that is required to definitively show that extracellular RNAs are functional in recipient cells in vivo.

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