Identification of an optimized 2′-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Felix CF Schmitt
  • Isabel Freund
  • Markus A Weigand
  • 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:000407850200004&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1261/rna.061952.117
eISSN
1469-9001
Externe Identifier
  • Clarivate Analytics Document Solution ID: FD9NW
  • PubMed Identifier: 28576825
ISSN
1355-8382
Ausgabe der Veröffentlichung
9
Zeitschrift
RNA
Schlüsselwörter
  • immune stimulation
  • TLR7
  • TLR8
  • inhibitory RNA
  • RNA modification
  • 2 '-O-methylation
Paginierung
1344 - 1351
Datum der Veröffentlichung
2017
Status
Published
Titel
Identification of an optimized 2′-<i>O</i>-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8
Sub types
  • Article
Ausgabe der Zeitschrift
23

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:p>Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between “host” and “foreign” RNA. Ribose 2′-<jats:italic>O</jats:italic>-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2′-<jats:italic>O</jats:italic>-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2′-<jats:italic>O</jats:italic>-methylated RNA sequence, we performed a systematic permutation of the methylated nucleotide as well as adjacent bases and hereby identify two minimal trinucleotide motifs within a 9-mer oligoribonucleotide that are necessary and sufficient to antagonize TLR7 and TLR8 activation, respectively. Given the growing interest in the development of inhibitors of nucleic acid-sensing TLRs for therapeutic purposes, these results will facilitate the rational design of such antagonists in the future.</jats:p>
Autoren
  • Felix CF Schmitt
  • Isabel Freund
  • Markus A Weigand
  • Mark Helm
  • Alexander H Dalpke
  • Tatjana Eigenbrod
DOI
10.1261/rna.061952.117
eISSN
1469-9001
ISSN
1355-8382
Ausgabe der Veröffentlichung
9
Zeitschrift
RNA
Sprache
en
Online publication date
2017
Paginierung
1344 - 1351
Datum der Veröffentlichung
2017
Status
Published
Herausgeber
Cold Spring Harbor Laboratory
Herausgeber URL
http://dx.doi.org/10.1261/rna.061952.117
Datum der Datenerfassung
2021
Titel
Identification of an optimized 2′-<i>O</i>-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8
Ausgabe der Zeitschrift
23

Datenquelle: Crossref

Abstract
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between "host" and "foreign" RNA. Ribose 2'-<i>O</i>-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-<i>O</i>-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2'-<i>O</i>-methylated RNA sequence, we performed a systematic permutation of the methylated nucleotide as well as adjacent bases and hereby identify two minimal trinucleotide motifs within a 9-mer oligoribonucleotide that are necessary and sufficient to antagonize TLR7 and TLR8 activation, respectively. Given the growing interest in the development of inhibitors of nucleic acid-sensing TLRs for therapeutic purposes, these results will facilitate the rational design of such antagonists in the future.
Addresses
  • Department of Anesthesiology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Autoren
  • Felix CF Schmitt
  • Isabel Freund
  • Markus A Weigand
  • Mark Helm
  • Alexander H Dalpke
  • Tatjana Eigenbrod
DOI
10.1261/rna.061952.117
eISSN
1469-9001
Externe Identifier
  • PubMed Identifier: 28576825
  • PubMed Central ID: PMC5558904
Funding acknowledgements
  • German Research Foundation: HE3397/9-1
  • German Research Foundation: DA592/5
  • German Center for Infection Research:
Open access
true
ISSN
1355-8382
Ausgabe der Veröffentlichung
9
Zeitschrift
RNA (New York, N.Y.)
Schlüsselwörter
  • Leukocytes, Mononuclear
  • Humans
  • Nucleotides
  • RNA
  • RNA, Bacterial
  • RNA, Transfer
  • Cytidine
  • Inhibitory Concentration 50
  • Methylation
  • Mutation
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Nucleotide Motifs
Sprache
eng
Medium
Print-Electronic
Online publication date
2017
Open access status
Open Access
Paginierung
1344 - 1351
Datum der Veröffentlichung
2017
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2017
Titel
Identification of an optimized 2'-<i>O</i>-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
23

Files

http://rnajournal.cshlp.org/content/23/9/1344.full.pdf https://europepmc.org/articles/PMC5558904?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Bacterial RNA serves an important function as activator of the innate immune system. In humans bacterial RNA is sensed by the endosomal receptors TLR7 and TLR8. Differences in the posttranscriptional modification profile of prokaryotic when compared with eukaryotic RNA allow innate immune cells to discriminate between "host" and "foreign" RNA. Ribose 2'-O-methylation is of particular importance and has been reported to antagonize TLR7/8 activation. Yet, the exact sequence context in which 2'-O-methylation has to occur to mediate its inhibitory activity remains largely undefined. On the basis of a naturally occurring 2'-O-methylated RNA sequence, we performed a systematic permutation of the methylated nucleotide as well as adjacent bases and hereby identify two minimal trinucleotide motifs within a 9-mer oligoribonucleotide that are necessary and sufficient to antagonize TLR7 and TLR8 activation, respectively. Given the growing interest in the development of inhibitors of nucleic acid-sensing TLRs for therapeutic purposes, these results will facilitate the rational design of such antagonists in the future.
Date of acceptance
2017
Autoren
  • Felix CF Schmitt
  • Isabel Freund
  • Markus A Weigand
  • Mark Helm
  • Alexander H Dalpke
  • Tatjana Eigenbrod
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/28576825
DOI
10.1261/rna.061952.117
eISSN
1469-9001
Externe Identifier
  • PubMed Central ID: PMC5558904
Ausgabe der Veröffentlichung
9
Zeitschrift
RNA
Schlüsselwörter
  • 2′-O-methylation
  • RNA modification
  • TLR7
  • TLR8
  • immune stimulation
  • inhibitory RNA
  • Cytidine
  • Humans
  • Inhibitory Concentration 50
  • Leukocytes, Mononuclear
  • Methylation
  • Mutation
  • Nucleotide Motifs
  • Nucleotides
  • RNA
  • RNA, Bacterial
  • RNA, Transfer
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
Sprache
eng
Country
United States
Paginierung
1344 - 1351
PII
rna.061952.117
Datum der Veröffentlichung
2017
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2017
Titel
Identification of an optimized 2'-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
23

Datenquelle: PubMed

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