Cargando…

Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System

The exchange of extracellular vesicles (EV) between immune cells plays a role in various immune regulatory processes. EV are nano-sized lipid bilayer-enclosed structures that contain a multitude of proteins and small non-coding RNA molecules. Of the various RNA classes present in EV, miRNAs have bee...

Descripción completa

Detalles Bibliográficos
Autores principales: Driedonks, Tom A. P., Nolte-'t Hoen, Esther N. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340977/
https://www.ncbi.nlm.nih.gov/pubmed/30697216
http://dx.doi.org/10.3389/fimmu.2018.03164
_version_ 1783388868569989120
author Driedonks, Tom A. P.
Nolte-'t Hoen, Esther N. M.
author_facet Driedonks, Tom A. P.
Nolte-'t Hoen, Esther N. M.
author_sort Driedonks, Tom A. P.
collection PubMed
description The exchange of extracellular vesicles (EV) between immune cells plays a role in various immune regulatory processes. EV are nano-sized lipid bilayer-enclosed structures that contain a multitude of proteins and small non-coding RNA molecules. Of the various RNA classes present in EV, miRNAs have been most intensively studied because of their known gene-regulatory functions. These miRNAs constitute only a minor part of all EV-enclosed RNA, whereas other 20–200 nt sized non-coding RNAs were shown to be abundantly present in EV. Several of these mid-sized RNAs perform basic functions in cells, but their function in EV remains elusive. One prominent class of mid-sized extracellular RNAs associated with EV are the Y-RNAs. This family of highly conserved non-coding RNAs was initially discovered as RNA component of circulating ribonucleoprotein autoantigens in serum from Systemic Lupus Erythematosus and Sjögren's Syndrome patients. Y-RNA has been implicated in cellular processes such as DNA replication and RNA quality control. In recent years, Y-RNA has been abundantly detected in EV from multiple different cell lines and biofluids, and also in murine and human retroviruses. Accumulating evidence suggests that EV-associated Y-RNA may be involved in a range of immune-related processes, including inflammation, immune suppression, and establishment of the tumor microenvironment. Moreover, changes in plasma levels of extracellular Y-RNA have been associated with various diseases. Recent studies have aimed to address the mechanisms underlying their release and function. We for example showed that the levels of EV-associated Y-RNA released by immune cells can be regulated by Toll-like receptor (TLR) signaling. Combined, these data have triggered increased interest in extracellular Y-RNAs. In this review, we provide an overview of studies reporting the occurrence of extracellular Y-RNAs, as well as signaling properties and immune-related functions attributed to these RNAs. We list RNA-binding proteins currently known to interact with Y-RNAs and evaluate their occurrence in EV. In parallel, we discuss technical challenges in assessing whether extracellular Y-RNAs are contained in ribonucleoprotein complexes or EV. By integrating the current knowledge on extracellular Y-RNA we further reflect on the biomarker potential of Y-RNA and their role in immune cell communication and immunopathology.
format Online
Article
Text
id pubmed-6340977
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-63409772019-01-29 Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System Driedonks, Tom A. P. Nolte-'t Hoen, Esther N. M. Front Immunol Immunology The exchange of extracellular vesicles (EV) between immune cells plays a role in various immune regulatory processes. EV are nano-sized lipid bilayer-enclosed structures that contain a multitude of proteins and small non-coding RNA molecules. Of the various RNA classes present in EV, miRNAs have been most intensively studied because of their known gene-regulatory functions. These miRNAs constitute only a minor part of all EV-enclosed RNA, whereas other 20–200 nt sized non-coding RNAs were shown to be abundantly present in EV. Several of these mid-sized RNAs perform basic functions in cells, but their function in EV remains elusive. One prominent class of mid-sized extracellular RNAs associated with EV are the Y-RNAs. This family of highly conserved non-coding RNAs was initially discovered as RNA component of circulating ribonucleoprotein autoantigens in serum from Systemic Lupus Erythematosus and Sjögren's Syndrome patients. Y-RNA has been implicated in cellular processes such as DNA replication and RNA quality control. In recent years, Y-RNA has been abundantly detected in EV from multiple different cell lines and biofluids, and also in murine and human retroviruses. Accumulating evidence suggests that EV-associated Y-RNA may be involved in a range of immune-related processes, including inflammation, immune suppression, and establishment of the tumor microenvironment. Moreover, changes in plasma levels of extracellular Y-RNA have been associated with various diseases. Recent studies have aimed to address the mechanisms underlying their release and function. We for example showed that the levels of EV-associated Y-RNA released by immune cells can be regulated by Toll-like receptor (TLR) signaling. Combined, these data have triggered increased interest in extracellular Y-RNAs. In this review, we provide an overview of studies reporting the occurrence of extracellular Y-RNAs, as well as signaling properties and immune-related functions attributed to these RNAs. We list RNA-binding proteins currently known to interact with Y-RNAs and evaluate their occurrence in EV. In parallel, we discuss technical challenges in assessing whether extracellular Y-RNAs are contained in ribonucleoprotein complexes or EV. By integrating the current knowledge on extracellular Y-RNA we further reflect on the biomarker potential of Y-RNA and their role in immune cell communication and immunopathology. Frontiers Media S.A. 2019-01-15 /pmc/articles/PMC6340977/ /pubmed/30697216 http://dx.doi.org/10.3389/fimmu.2018.03164 Text en Copyright © 2019 Driedonks and Nolte-'t Hoen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Driedonks, Tom A. P.
Nolte-'t Hoen, Esther N. M.
Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title_full Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title_fullStr Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title_full_unstemmed Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title_short Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System
title_sort circulating y-rnas in extracellular vesicles and ribonucleoprotein complexes; implications for the immune system
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340977/
https://www.ncbi.nlm.nih.gov/pubmed/30697216
http://dx.doi.org/10.3389/fimmu.2018.03164
work_keys_str_mv AT driedonkstomap circulatingyrnasinextracellularvesiclesandribonucleoproteincomplexesimplicationsfortheimmunesystem
AT noltethoenesthernm circulatingyrnasinextracellularvesiclesandribonucleoproteincomplexesimplicationsfortheimmunesystem