Export of microRNAs and microRNA-protective protein by mammalian cells
Open accessAbstract
The discovery of microRNAs (miRNAs) as a new class of regulators of gene expression has triggered an explosion of research activities, but has left many unanswered questions about how this regulation functions and how it is integrated with other regulatory mechanisms. A number of miRNAs have been found to be present in plasma and other body fluids of humans and mice in surprisingly high concentrations. This observation was unexpected in two respects: first, the fact that these molecules are present at all outside the cell at significant concentrations and second, that these molecules appear to be stable outside of the cell. In light of this it has been suggested that the biological function of miRNAs may also extend outside of the cell and mediate cell-cell communication. We report here that after serum deprivation several human cell lines tested promptly export a substantial amount of miRNAs into the culture medium and the export process is largely energy dependent. The exported miRNAs are found both within and outside of the 16.5 and 120 K centrifugation pellets which contain most of the known cell-derived vesicles, the microvesicles and exosomes. We have identified some candidate proteins involved in this system, and one of these proteins may also play a role in protecting extracellular miRNAs from degradation. Our results point to a hitherto unrecognized and uncharacterized miRNA trafficking system in mammalian cells that is consistent with the cell-cell communication hypothesis.
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Other proteins found to bind extracellular miRNAs include high-density lipoprotein and nucleophosmin 1.
“Other proteins found to bind extracellular miRNAs include high-density lipoprotein (HDL) (126, 127) and nucleophosmin 1 (NPM1) (110, 118, 128).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [110]
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- Authors
- Wang, K., Zhang, S., Weber, J., Baxter, D., & Galas, D. J.
- Affiliations
- Institute for Systems Biology (US)
- Corresponding author
- Galas, David J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-07-07
- Volume
- 38
- Issue
- 20
- Pages
- 7248-7259
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC2978372
- OpenAlex
- W2003206209
- Cited by
- 1,002
- References
- 37
- Citations by year
- 2026: 15 · 2025: 21 · 2024: 30 · 2023: 35 · 2022: 46 · 2021: 67 · 2020: 76 · 2019: 61 · 2018: 76 · 2017: 69 · 2016: 87 · 2015: 87 · 2014: 98 · 2013: 94 · 2012: 87
- FWCI
- 30.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Battelle
- Ohio State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- extracellular microRNAs, serum deprivation, intercellular communication, microvesicles, exosomes, extracellular vesicles, miRNA stability
- MeSH terms
- Nucleophosmin, Adenosine Triphosphate, Cell Communication, Cell Line, Humans, Nuclear Proteins, RNA-Binding Proteins, Culture Media, Serum-Free, RNA Stability, RNA Transport, MicroRNAs
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