Tags

Type your tag names separated by a space and hit enter

Stable tRNA halves can be sorted into extracellular vesicles and delivered to recipient cells in a concentration-dependent manner.
RNA Biol. 2020 Aug; 17(8):1168-1182.RB

Abstract

Extracellular vesicles (EVs) are cell-derived nanoparticles that act as natural carriers of nucleic acids between cells. They offer advantages as delivery vehicles for therapeutic nucleic acids such as small RNAs. Loading of desired nucleic acids into EVs can be achieved by electroporation or transfection once purified. An attractive alternative is to transfect cells with the desired small RNAs and harness the cellular machinery for RNA sorting into the EVs. This possibility has been less explored because cells are believed to secrete only specific RNAs. However, we hypothesized that, even in the presence of selective secretion, concentration-driven RNA sorting to EVs would still be feasible. To show this, we transfected cells with glycine 5' tRNA halves, which we have previously shown to better resist RNases. We then measured their levels in EVs and in recipient cells and found that, in contrast to unstable RNAs of random sequence, these tRNA halves were present in vesicles and in recipient cells in amounts proportional to the concentration of RNA used for transfection. Similar efficiencies were obtained with other stable oligonucleotides of random sequence. Our results demonstrate that RNA stability is a key factor needed to maintain high intracellular concentrations, a prerequisite for efficient non-selective RNA sorting to EVs and delivery to cells. Given that glycine 5' tRNA halves belong to the group of stress-induced tRNA fragments frequently detected in extracellular space and biofluids, we propose that upregulation of extracellular tRNA fragments is consequential to cellular stress and might be involved in intercellular signalling.

Authors+Show Affiliations

Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay. Molecular Virology Laboratory, Nuclear Research Center, Faculty of Science, Universidad de la República , Montevideo, Uruguay.Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay.Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay. Analytical Biochemistry Unit, Nuclear Research Center, Faculty of Science, Universidad de la República , Montevideo, Uruguay.Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay. Analytical Biochemistry Unit, Nuclear Research Center, Faculty of Science, Universidad de la República , Montevideo, Uruguay.Molecular Biology Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay.Molecular and Comparative Pathobiology, and Neurology, The Johns Hopkins University School of Medicine , Baltimore, MD, USA.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital , Boston, MA, USA. Department of Medicine, Harvard Medical School , Boston, MA, USA. Department of Biochemistry, and The Genome Science Institute, Boston University School of Medicine , Boston, MA, USA.Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital , Boston, MA, USA. Department of Medicine, Harvard Medical School , Boston, MA, USA. The Broad Institute of Harvard and M.I.T ., Cambridge, MA, USA.Molecular and Comparative Pathobiology, and Neurology, The Johns Hopkins University School of Medicine , Baltimore, MD, USA.Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay. Department of Medicine, Faculty of Medicine, Universidad de la República , Montevideo, Uruguay.Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo, Uruguay. Analytical Biochemistry Unit, Nuclear Research Center, Faculty of Science, Universidad de la República , Montevideo, Uruguay.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31885318

Citation

Gámbaro, Fabiana, et al. "Stable tRNA Halves Can Be Sorted Into Extracellular Vesicles and Delivered to Recipient Cells in a Concentration-dependent Manner." RNA Biology, vol. 17, no. 8, 2020, pp. 1168-1182.
Gámbaro F, Li Calzi M, Fagúndez P, et al. Stable tRNA halves can be sorted into extracellular vesicles and delivered to recipient cells in a concentration-dependent manner. RNA Biol. 2020;17(8):1168-1182.
Gámbaro, F., Li Calzi, M., Fagúndez, P., Costa, B., Greif, G., Mallick, E., Lyons, S., Ivanov, P., Witwer, K., Cayota, A., & Tosar, J. P. (2020). Stable tRNA halves can be sorted into extracellular vesicles and delivered to recipient cells in a concentration-dependent manner. RNA Biology, 17(8), 1168-1182. https://doi.org/10.1080/15476286.2019.1708548
Gámbaro F, et al. Stable tRNA Halves Can Be Sorted Into Extracellular Vesicles and Delivered to Recipient Cells in a Concentration-dependent Manner. RNA Biol. 2020;17(8):1168-1182. PubMed PMID: 31885318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stable tRNA halves can be sorted into extracellular vesicles and delivered to recipient cells in a concentration-dependent manner. AU - Gámbaro,Fabiana, AU - Li Calzi,Marco, AU - Fagúndez,Pablo, AU - Costa,Bruno, AU - Greif,Gonzalo, AU - Mallick,Emily, AU - Lyons,Shawn, AU - Ivanov,Pavel, AU - Witwer,Kenneth, AU - Cayota,Alfonso, AU - Tosar,Juan Pablo, Y1 - 2019/12/29/ PY - 2019/12/31/pubmed PY - 2019/12/31/medline PY - 2019/12/31/entrez KW - exosomes KW - intercellular communication KW - secretion KW - tiRNAs KW - vesicles SP - 1168 EP - 1182 JF - RNA biology JO - RNA Biol VL - 17 IS - 8 N2 - Extracellular vesicles (EVs) are cell-derived nanoparticles that act as natural carriers of nucleic acids between cells. They offer advantages as delivery vehicles for therapeutic nucleic acids such as small RNAs. Loading of desired nucleic acids into EVs can be achieved by electroporation or transfection once purified. An attractive alternative is to transfect cells with the desired small RNAs and harness the cellular machinery for RNA sorting into the EVs. This possibility has been less explored because cells are believed to secrete only specific RNAs. However, we hypothesized that, even in the presence of selective secretion, concentration-driven RNA sorting to EVs would still be feasible. To show this, we transfected cells with glycine 5' tRNA halves, which we have previously shown to better resist RNases. We then measured their levels in EVs and in recipient cells and found that, in contrast to unstable RNAs of random sequence, these tRNA halves were present in vesicles and in recipient cells in amounts proportional to the concentration of RNA used for transfection. Similar efficiencies were obtained with other stable oligonucleotides of random sequence. Our results demonstrate that RNA stability is a key factor needed to maintain high intracellular concentrations, a prerequisite for efficient non-selective RNA sorting to EVs and delivery to cells. Given that glycine 5' tRNA halves belong to the group of stress-induced tRNA fragments frequently detected in extracellular space and biofluids, we propose that upregulation of extracellular tRNA fragments is consequential to cellular stress and might be involved in intercellular signalling. SN - 1555-8584 UR - https://www.unboundmedicine.com/medline/citation/31885318/Stable_tRNA_halves_can_be_sorted_into_extracellular_vesicles_and_delivered_to_recipient_cells_in_a_concentration_dependent_manner_ L2 - http://www.tandfonline.com/doi/full/10.1080/15476286.2019.1708548 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.