Revisiting extracellular RNA release, processing, and function
Open accessAbstract
It is assumed that RNAs enriched in extracellular samples were selected for release by their parental cells. However, recent descriptions of extracellular RNA (exRNA) biogenesis and their differential stabilities question this assumption, as they could produce identical outcomes. Here, we share our opinion about the importance of considering both selective and nonselective mechanisms for RNA release into the extracellular environment. In doing so, we provide new perspectives on RNA-mediated intercellular communication, including an analogy to communication through social media. We also argue that technical limitations have restricted the study of some of the most abundant exRNAs, both inside and outside extracellular vesicles (EVs). These RNAs may be better positioned to induce a response in recipient cells compared with low abundance miRNAs.
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Circulating miRNA research has not resulted in any highly specific, validated disease markers.
“circulating miRNA research has not resulted in any highly specific, validated disease markers (Tosar et al., 2021; Witwer, 2015).”
From Small nucleolar RNAs in plasma extracellular vesicles and their discriminatory power as diagnostic biomarkers of Alzheimer's disease (2021) · cites this paper as Tosar et al., 2021
The 'Extracellular RNA dynamics' section calls extracellular RNAs promising sources of disease biomarkers, while 'Sorting RNAs to the extracellular space: how?' discusses contamination that can distort miRNA analyses. Neither section addresses whether circulating miRNA research has produced highly specific, validated disease markers (searched: biomarkers, validation, and specificity). No page numbers were available in our copy. (LLM, conf=0.75)
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Self-citationA Network of Macrophages Supports Mitochondrial Homeostasis in the Heart
Nicolás-Ávila, J. A., Lechuga-Vieco, A. V., Esteban-Martínez, L., Sánchez-Díaz, M., Díaz-García, E., Santiago, D. J., Rubio-Ponce, A., Li, J. L., Balachander, A., Quintana, J. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.031 · Cited by 762 · see citing works
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Extracellular Vesicles and Nanoparticles: Emerging Complexities
Jeppesen, D. K., Zhang, Q., Franklin, J. L., & Coffey, R. J. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.01.002 · Cited by 705 · see citing works
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“While there is no definitive conclusion if a specific miRNA or set of miRNAs exist for certain pathological condition(s), circulating miRNA research has not resulted in any highly specific, validated disease markers (Tosar et al., 2021; Witwer, 2015).”
Shanthi, K., Fischer, D., Sharma, A., Kiviniemi, A., Kaakinen, M., Vainio, S., & Bart, G. (2023) · Genes · doi:10.3390/genes14040853 · Cited by 5 · see citing works
- Authors
- Tosar, J. P., Witwer, K., & Cayota, A.
- Affiliations
- Universidad de la República de Uruguay (UY)
- Johns Hopkins University (US)
- Corresponding author
- Tosar, Juan Pablo
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 46
- Issue
- 6
- Pages
- 438-445
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC8122015
- OpenAlex
- W3120963541
- Cited by
- 91
- References
- 2
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 12
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Universidad de la República Uruguay
- NIH Office of the Director (UG3CA241694)
- Agencia Nacional de Investigación e Innovación (FCE_3_2018_1_148745)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- extracellular RNA, RNA release, extracellular vesicles, RNA biogenesis, RNA stability, intercellular communication, microRNA
- MeSH terms
- Extracellular Vesicles, Cell Communication, Humans, MicroRNAs
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