A modified dinucleotide motif specifies tRNA recognition by TLR7

Abstract

RNA can function as a pathogen-associated molecular pattern (PAMP) whose recognition by the innate immune system alerts the body to an impending microbial infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends on its modification patterns. In particular, it is known that the presence of a ribose methylated guanosine at position 18, which is overrepresented in self-RNA, antagonizes an immune response. Here, we report that recognition extends to the next downstream nucleotide and the effectively recognized molecular detail is actually a methylated dinucleotide. The most efficient nucleobases combination of this motif includes two purines, while pyrimidines diminish the effect of ribose methylation. The constraints of this motif stay intact when transposed to other parts of the tRNA. The results argue against a fixed orientation of the tRNA during interaction with TLR7 and, rather, suggest a processive type of inspection.

Autoren

Steffen Kaiser
Katharina Rimbach
Tatjana Eigenbrod
Alexander H Dalpke
Mark Helm

DOI

10.1261/rna.044024.113

eISSN

1469-9001

ISSN

1355-8382

Ausgabe der Veröffentlichung

9

Zeitschrift

RNA

Sprache

en

Online publication date

2014

Paginierung

1351 - 1355

Datum der Veröffentlichung

2014

Status

Published

Herausgeber

Cold Spring Harbor Laboratory

Herausgeber URL

http://dx.doi.org/10.1261/rna.044024.113

Datum der Datenerfassung

2021

Titel

A modified dinucleotide motif specifies tRNA recognition by TLR7

Ausgabe der Zeitschrift

20

Data source: Crossref

Abstract

RNA can function as a pathogen-associated molecular pattern (PAMP) whose recognition by the innate immune system alerts the body to an impending microbial infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends on its modification patterns. In particular, it is known that the presence of a ribose methylated guanosine at position 18, which is overrepresented in self-RNA, antagonizes an immune response. Here, we report that recognition extends to the next downstream nucleotide and the effectively recognized molecular detail is actually a methylated dinucleotide. The most efficient nucleobases combination of this motif includes two purines, while pyrimidines diminish the effect of ribose methylation. The constraints of this motif stay intact when transposed to other parts of the tRNA. The results argue against a fixed orientation of the tRNA during interaction with TLR7 and, rather, suggest a processive type of inspection.

Addresses

Institute of Pharmacy and Biochemistry, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.

Autoren

Steffen Kaiser
Katharina Rimbach
Tatjana Eigenbrod
Alexander H Dalpke
Mark Helm

DOI

10.1261/rna.044024.113

eISSN

1469-9001

Externe Identifier

PubMed Identifier: 25051971
PubMed Central ID: PMC4138318

Funding acknowledgements

Deutsche Forschungsgemeinschaft: 592/5
Deutsche Forschungsgemeinschaft: HE 3397/9

Open access

true

ISSN

1355-8382

Ausgabe der Veröffentlichung

9

Zeitschrift

RNA (New York, N.Y.)

Schlüsselwörter

Cells, Cultured
Humans
RNA, Transfer
Binding Sites
Base Sequence
Nucleic Acid Conformation
Protein Binding
Substrate Specificity
Models, Molecular
Molecular Sequence Data
Toll-Like Receptor 7

Sprache

eng

Medium

Print-Electronic

Online publication date

2014

Open access status

Open Access

Paginierung

1351 - 1355

Datum der Veröffentlichung

2014

Status

Published

Publisher licence

CC BY-NC

Datum der Datenerfassung

2014

Titel

A modified dinucleotide motif specifies tRNA recognition by TLR7.

Sub types

Letter
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

20

Files

http://rnajournal.cshlp.org/content/20/9/1351.full.pdf https://europepmc.org/articles/PMC4138318?pdf=render

Data source: Europe PubMed Central

Abstract

RNA can function as a pathogen-associated molecular pattern (PAMP) whose recognition by the innate immune system alerts the body to an impending microbial infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends on its modification patterns. In particular, it is known that the presence of a ribose methylated guanosine at position 18, which is overrepresented in self-RNA, antagonizes an immune response. Here, we report that recognition extends to the next downstream nucleotide and the effectively recognized molecular detail is actually a methylated dinucleotide. The most efficient nucleobases combination of this motif includes two purines, while pyrimidines diminish the effect of ribose methylation. The constraints of this motif stay intact when transposed to other parts of the tRNA. The results argue against a fixed orientation of the tRNA during interaction with TLR7 and, rather, suggest a processive type of inspection.

Autoren

Steffen Kaiser
Katharina Rimbach
Tatjana Eigenbrod
Alexander H Dalpke
Mark Helm

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/25051971

DOI

10.1261/rna.044024.113

eISSN

1469-9001

Externe Identifier

PubMed Central ID: PMC4138318

Ausgabe der Veröffentlichung

9

Zeitschrift

RNA

Schlüsselwörter

RNA modification
TLR7
immunostimulation
innate immunity
ribose methylation
Base Sequence
Binding Sites
Cells, Cultured
Humans
Models, Molecular
Molecular Sequence Data
Nucleic Acid Conformation
Protein Binding
RNA, Transfer
Substrate Specificity
Toll-Like Receptor 7

Sprache

eng

Country

United States

Paginierung

1351 - 1355

PII

rna.044024.113

Datum der Veröffentlichung

2014

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2014

Titel

A modified dinucleotide motif specifies tRNA recognition by TLR7.

Sub types

Letter
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

20

Data source: PubMed

A modified dinucleotide motif specifies tRNA recognition by TLR7

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