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Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation

The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs release...

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Detalles Bibliográficos
Autores principales: Chiou, Ni-Ting, Kageyama, Robin, Ansel, K. Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392044/
https://www.ncbi.nlm.nih.gov/pubmed/30566862
http://dx.doi.org/10.1016/j.celrep.2018.11.073
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author Chiou, Ni-Ting
Kageyama, Robin
Ansel, K. Mark
author_facet Chiou, Ni-Ting
Kageyama, Robin
Ansel, K. Mark
author_sort Chiou, Ni-Ting
collection PubMed
description The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs released by T cells, we found that 45% of tRNA fragments (tRFs), but fewer than 1% of miRNAs, were significantly enriched in EVs compared with the corresponding cellular RNA. T cell activation induced the EV-mediated release of a specific set of tRFs derived from the 5′ end and 3′-internal region of tRNAs without variable loops. Inhibition of EV biogenesis pathways specifically led to the accumulation of these activation-induced EV-enriched tRFs within multivesicular bodies (MVBs). Introducing antisense oligonucleotides to inhibit these tRFs enhanced T cell activation. Taken together, these results demonstrate that T cells selectively release tRFs into EVs via MVBs and suggest that this process may remove tRFs that repress immune activation.
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spelling pubmed-63920442019-02-27 Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation Chiou, Ni-Ting Kageyama, Robin Ansel, K. Mark Cell Rep Article The discovery of microRNA (miRNA) sorting into extracellular vesicles (EVs) revealed a novel mode of intercellular communication and uncovered a link between cellular endomembrane compartments and small RNAs in EV-secreting cells. Using a two-step ultracentrifugation procedure to isolate EVs released by T cells, we found that 45% of tRNA fragments (tRFs), but fewer than 1% of miRNAs, were significantly enriched in EVs compared with the corresponding cellular RNA. T cell activation induced the EV-mediated release of a specific set of tRFs derived from the 5′ end and 3′-internal region of tRNAs without variable loops. Inhibition of EV biogenesis pathways specifically led to the accumulation of these activation-induced EV-enriched tRFs within multivesicular bodies (MVBs). Introducing antisense oligonucleotides to inhibit these tRFs enhanced T cell activation. Taken together, these results demonstrate that T cells selectively release tRFs into EVs via MVBs and suggest that this process may remove tRFs that repress immune activation. 2018-12-18 /pmc/articles/PMC6392044/ /pubmed/30566862 http://dx.doi.org/10.1016/j.celrep.2018.11.073 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Chiou, Ni-Ting
Kageyama, Robin
Ansel, K. Mark
Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title_full Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title_fullStr Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title_full_unstemmed Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title_short Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
title_sort selective export into extracellular vesicles and function of trna fragments during t cell activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392044/
https://www.ncbi.nlm.nih.gov/pubmed/30566862
http://dx.doi.org/10.1016/j.celrep.2018.11.073
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