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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...

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Autores principales: Nicolai, Marina, Steinberg, Julia, Obermann, Hannah-Lena, Solis, Francisco Venegas, Bartok, Eva, Bauer, Stefan, Jung, Stephanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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