2′-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Isabel Freund
- Daniel K Buhl
- Sebastien Boutin
- Annika Kotter
- Florian Pichot
- Virginie Marchand
- Tim Vierbuchen
- Holger Heine
- Yuri Motorin
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000471827600009&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1261/rna.070243.118
- eISSN
- 1469-9001
- Externe Identifier
- Clarivate Analytics Document Solution ID: ID6YG
- PubMed Identifier: 31019095
- ISSN
- 1355-8382
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- RNA
- Schlüsselwörter
- immune stimulation
- bacterial RNA
- TLR
- RNA modification
- 2&PRIME-O-methylation
- Paginierung
- 869 - 880
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Titel
- 2′-<i>O</i>-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms
- Sub types
- Article
- Ausgabe der Zeitschrift
- 25
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>Bacterial RNA has emerged as an important activator of innate immune responses by stimulating Toll-like receptors TLR7 and TLR8 in humans. Guanosine 2′-<jats:italic>O</jats:italic>-methylation at position 18 (Gm18) in bacterial tRNA was shown to antagonize tRNA-induced TLR7/8 activation, suggesting a potential role of Gm18 as an immune escape mechanism. This modification also occurs in eukaryotic tRNA, yet a physiological immune function remained to be tested. We therefore set out to investigate the immune modulatory role of Gm18 in both prokaryotic and eukaryotic microorganisms, <jats:italic>Escherichia coli</jats:italic> and <jats:italic>Saccharomyces cerevisiae</jats:italic>, and in human cells. Using RiboMethSeq analysis we show that mutation of <jats:italic>trmH</jats:italic> in <jats:italic>E. coli</jats:italic>, <jats:italic>trm3</jats:italic> in <jats:italic>S. cereviase</jats:italic>, and CRISPR/Cas9-induced knockout of <jats:italic>TARBP1</jats:italic> in <jats:italic>H. sapiens</jats:italic> results in loss of Gm18 within tRNA. Lack of Gm18 across the kingdoms resulted in increased immunostimulation of peripheral blood mononuclear cells when activated by tRNA preparations. In <jats:italic>E. coli</jats:italic>, lack of 2′-<jats:italic>O</jats:italic>-methyltransferase trmH also enhanced immune stimulatory properties by whole cellular RNA. In contrast, lack of Gm18 in yeasts and human cells did not affect immunostimulation by whole RNA preparations. When using live <jats:italic>E. coli</jats:italic> bacteria, lack of <jats:italic>trmH</jats:italic> did not affect overall immune stimulation although we detected a defined TLR8/RNA-dependent gene expression signature upon <jats:italic>E. coli</jats:italic> infection. Together, these results demonstrate that Gm18 is a global immune inhibitory tRNA modification across the kingdoms and contributes to tRNA recognition by innate immune cells, but as an individual modification has insufficient potency to modulate recognition of the investigated microorganisms.</jats:p>
- Autoren
- Isabel Freund
- Daniel K Buhl
- Sébastien Boutin
- Annika Kotter
- Florian Pichot
- Virginie Marchand
- Tim Vierbuchen
- Holger Heine
- Yuri Motorin
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- DOI
- 10.1261/rna.070243.118
- eISSN
- 1469-9001
- ISSN
- 1355-8382
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- RNA
- Sprache
- en
- Online publication date
- 2019
- Paginierung
- 869 - 880
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Herausgeber
- Cold Spring Harbor Laboratory
- Herausgeber URL
- http://dx.doi.org/10.1261/rna.070243.118
- Datum der Datenerfassung
- 2021
- Titel
- 2′-<i>O</i>-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms
- Ausgabe der Zeitschrift
- 25
Datenquelle: Crossref
- Abstract
- Bacterial RNA has emerged as an important activator of innate immune responses by stimulating Toll-like receptors TLR7 and TLR8 in humans. Guanosine 2'-<i>O</i>-methylation at position 18 (Gm18) in bacterial tRNA was shown to antagonize tRNA-induced TLR7/8 activation, suggesting a potential role of Gm18 as an immune escape mechanism. This modification also occurs in eukaryotic tRNA, yet a physiological immune function remained to be tested. We therefore set out to investigate the immune modulatory role of Gm18 in both prokaryotic and eukaryotic microorganisms, <i>Escherichia coli</i> and <i>Saccharomyces cerevisiae</i>, and in human cells. Using RiboMethSeq analysis we show that mutation of <i>trmH</i> in <i>E. coli</i>, <i>trm3</i> in <i>S. cereviase</i>, and CRISPR/Cas9-induced knockout of <i>TARBP1</i> in <i>H. sapiens</i> results in loss of Gm18 within tRNA. Lack of Gm18 across the kingdoms resulted in increased immunostimulation of peripheral blood mononuclear cells when activated by tRNA preparations. In <i>E. coli</i>, lack of 2'-<i>O</i>-methyltransferase trmH also enhanced immune stimulatory properties by whole cellular RNA. In contrast, lack of Gm18 in yeasts and human cells did not affect immunostimulation by whole RNA preparations. When using live <i>E. coli</i> bacteria, lack of <i>trmH</i> did not affect overall immune stimulation although we detected a defined TLR8/RNA-dependent gene expression signature upon <i>E. coli</i> infection. Together, these results demonstrate that Gm18 is a global immune inhibitory tRNA modification across the kingdoms and contributes to tRNA recognition by innate immune cells, but as an individual modification has insufficient potency to modulate recognition of the investigated microorganisms.
- Addresses
- Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 69120 Heidelberg, Germany.
- Autoren
- Isabel Freund
- Daniel K Buhl
- Sébastien Boutin
- Annika Kotter
- Florian Pichot
- Virginie Marchand
- Tim Vierbuchen
- Holger Heine
- Yuri Motorin
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- DOI
- 10.1261/rna.070243.118
- eISSN
- 1469-9001
- Externe Identifier
- PubMed Identifier: 31019095
- PubMed Central ID: PMC6573781
- Funding acknowledgements
- German Research Foundation: DA592/5
- German Research Foundation: He 3397/18-1
- German Research Foundation: DA592
- Open access
- true
- ISSN
- 1355-8382
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- RNA (New York, N.Y.)
- Schlüsselwörter
- Endosomes
- Eukaryotic Cells
- Prokaryotic Cells
- Humans
- tRNA Methyltransferases
- RNA, Transfer
- Guanosine
- Methylation
- Toll-Like Receptors
- Immunity, Innate
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2019
- Open access status
- Open Access
- Paginierung
- 869 - 880
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Publisher licence
- CC BY-NC
- Datum der Datenerfassung
- 2019
- Titel
- 2'-<i>O</i>-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms.
- Sub types
- Research Support, Non-U.S. Gov't
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 25
Files
http://rnajournal.cshlp.org/content/25/7/869.full.pdf https://europepmc.org/articles/PMC6573781?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Bacterial RNA has emerged as an important activator of innate immune responses by stimulating Toll-like receptors TLR7 and TLR8 in humans. Guanosine 2'-O-methylation at position 18 (Gm18) in bacterial tRNA was shown to antagonize tRNA-induced TLR7/8 activation, suggesting a potential role of Gm18 as an immune escape mechanism. This modification also occurs in eukaryotic tRNA, yet a physiological immune function remained to be tested. We therefore set out to investigate the immune modulatory role of Gm18 in both prokaryotic and eukaryotic microorganisms, Escherichia coli and Saccharomyces cerevisiae, and in human cells. Using RiboMethSeq analysis we show that mutation of trmH in E. coli, trm3 in S. cereviase, and CRISPR/Cas9-induced knockout of TARBP1 in H. sapiens results in loss of Gm18 within tRNA. Lack of Gm18 across the kingdoms resulted in increased immunostimulation of peripheral blood mononuclear cells when activated by tRNA preparations. In E. coli, lack of 2'-O-methyltransferase trmH also enhanced immune stimulatory properties by whole cellular RNA. In contrast, lack of Gm18 in yeasts and human cells did not affect immunostimulation by whole RNA preparations. When using live E. coli bacteria, lack of trmH did not affect overall immune stimulation although we detected a defined TLR8/RNA-dependent gene expression signature upon E. coli infection. Together, these results demonstrate that Gm18 is a global immune inhibitory tRNA modification across the kingdoms and contributes to tRNA recognition by innate immune cells, but as an individual modification has insufficient potency to modulate recognition of the investigated microorganisms.
- Date of acceptance
- 2019
- Autoren
- Isabel Freund
- Daniel K Buhl
- Sébastien Boutin
- Annika Kotter
- Florian Pichot
- Virginie Marchand
- Tim Vierbuchen
- Holger Heine
- Yuri Motorin
- Mark Helm
- Alexander H Dalpke
- Tatjana Eigenbrod
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31019095
- DOI
- 10.1261/rna.070243.118
- eISSN
- 1469-9001
- Externe Identifier
- PubMed Central ID: PMC6573781
- Ausgabe der Veröffentlichung
- 7
- Zeitschrift
- RNA
- Schlüsselwörter
- 2′-O-methylation
- RNA modification
- TLR
- bacterial RNA
- immune stimulation
- Endosomes
- Eukaryotic Cells
- Guanosine
- Humans
- Immunity, Innate
- Methylation
- Prokaryotic Cells
- RNA, Transfer
- Toll-Like Receptors
- tRNA Methyltransferases
- Sprache
- eng
- Country
- United States
- Paginierung
- 869 - 880
- PII
- rna.070243.118
- Datum der Veröffentlichung
- 2019
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2019
- Titel
- 2'-O-methylation within prokaryotic and eukaryotic tRNA inhibits innate immune activation by endosomal Toll-like receptors but does not affect recognition of whole organisms.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 25
Datenquelle: PubMed
- Beziehungen:
- Eigentum von