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Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation
Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2′-O-ribose (2′-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2′-O-methylation...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570189/ https://www.ncbi.nlm.nih.gov/pubmed/36232437 http://dx.doi.org/10.3390/ijms231911139 |
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author | Nicolai, Marina Steinberg, Julia Obermann, Hannah-Lena Solis, Francisco Venegas Bartok, Eva Bauer, Stefan Jung, Stephanie |
author_facet | Nicolai, Marina Steinberg, Julia Obermann, Hannah-Lena Solis, Francisco Venegas Bartok, Eva Bauer, Stefan Jung, Stephanie |
author_sort | Nicolai, Marina |
collection | PubMed |
description | Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2′-O-ribose (2′-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2′-O-methylation is crucial for its function. To this end, we designed different 2′-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2′-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2′-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2′-O-methylated RNA derivatives as optimal TLR8 ligands. |
format | Online Article Text |
id | pubmed-9570189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95701892022-10-17 Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation Nicolai, Marina Steinberg, Julia Obermann, Hannah-Lena Solis, Francisco Venegas Bartok, Eva Bauer, Stefan Jung, Stephanie Int J Mol Sci Article Recognition of RNA by receptors of the innate immune system is regulated by various posttranslational modifications. Different single 2′-O-ribose (2′-O-) methylations have been shown to convert TLR7/TLR8 ligands into specific TLR8 ligands, so we investigated whether the position of 2′-O-methylation is crucial for its function. To this end, we designed different 2′-O-methylated RNA oligoribonucleotides (ORN), investigating their immune activity in various cell systems and analyzing degradation under RNase T2 treatment. We found that the 18S rRNA-derived TLR7/8 ligand, RNA63, was differentially digested as a result of 2′-O-methylation, leading to variations in TLR8 and TLR7 inhibition. The suitability of certain 2′-O-methylated RNA63 derivatives as TLR8 agonists was further demonstrated by the fact that other RNA sequences were only weak TLR8 agonists. We were thus able to identify specific 2′-O-methylated RNA derivatives as optimal TLR8 ligands. MDPI 2022-09-22 /pmc/articles/PMC9570189/ /pubmed/36232437 http://dx.doi.org/10.3390/ijms231911139 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nicolai, Marina Steinberg, Julia Obermann, Hannah-Lena Solis, Francisco Venegas Bartok, Eva Bauer, Stefan Jung, Stephanie Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title | Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title_full | Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title_fullStr | Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title_full_unstemmed | Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title_short | Identification of an Optimal TLR8 Ligand by Alternating the Position of 2′-O-Ribose Methylation |
title_sort | identification of an optimal tlr8 ligand by alternating the position of 2′-o-ribose methylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570189/ https://www.ncbi.nlm.nih.gov/pubmed/36232437 http://dx.doi.org/10.3390/ijms231911139 |
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