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

Summary: 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 EV...

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Main Authors: Ni-Ting Chiou, Robin Kageyama, K. Mark Ansel
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718318497
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author Ni-Ting Chiou
Robin Kageyama
K. Mark Ansel
author_facet Ni-Ting Chiou
Robin Kageyama
K. Mark Ansel
author_sort Ni-Ting Chiou
collection DOAJ
description Summary: 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. : Chiou et al. show that T cells release extracellular vesicles that carry RNA cargo enriched in tRNA fragments. Immune activating signals enhance multivesicular body formation and the secretion of vesicles containing specific tRNA fragments. Within cells, these tRNA fragments inhibit T cell activation and cytokine production. Keywords: tRNA fragment, tsRNA, extracellular vesicle, exosome, T lymphocyte
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spelling doaj.art-ee28c613a42f4acb993e72c5f81bdd2c2022-12-22T01:45:45ZengElsevierCell Reports2211-12472018-12-01251233563370.e4Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell ActivationNi-Ting Chiou0Robin Kageyama1K. Mark Ansel2Sandler Asthma Basic Research Center and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USASandler Asthma Basic Research Center and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USASandler Asthma Basic Research Center and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA, USA; Corresponding authorSummary: 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. : Chiou et al. show that T cells release extracellular vesicles that carry RNA cargo enriched in tRNA fragments. Immune activating signals enhance multivesicular body formation and the secretion of vesicles containing specific tRNA fragments. Within cells, these tRNA fragments inhibit T cell activation and cytokine production. Keywords: tRNA fragment, tsRNA, extracellular vesicle, exosome, T lymphocytehttp://www.sciencedirect.com/science/article/pii/S2211124718318497
spellingShingle Ni-Ting Chiou
Robin Kageyama
K. Mark Ansel
Selective Export into Extracellular Vesicles and Function of tRNA Fragments during T Cell Activation
Cell Reports
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
url http://www.sciencedirect.com/science/article/pii/S2211124718318497
work_keys_str_mv AT nitingchiou selectiveexportintoextracellularvesiclesandfunctionoftrnafragmentsduringtcellactivation
AT robinkageyama selectiveexportintoextracellularvesiclesandfunctionoftrnafragmentsduringtcellactivation
AT kmarkansel selectiveexportintoextracellularvesiclesandfunctionoftrnafragmentsduringtcellactivation