TLR8 Is a Sensor of RNase T2 Degradation Products
2019-11-27
Wilhelm Greulich, Mirko Wagner, Moritz M. Gaidt, Che Stafford, Yiming Cheng, Andreas Linder, Thomas Carell, and Veit Hornung
TLR8 is among the highest-expressed pattern-recognition receptors in the human myeloid compartment, yet its mode of action is poorly understood. TLR8 engages two distinct ligand binding sites to sense RNA degradation products, although it remains unclear how these ligands are formed in cellulo in the context of complex RNA molecule sensing. Here, we identified the lysosomal endoribonuclease RNase T2 as a non-redundant upstream component of TLR8-dependent RNA recognition. RNase T2 activity is required for rendering complex single-stranded, exogenous RNA molecules detectable for TLR8. This is due to RNase T2’s preferential cleavage of single-stranded RNA molecules between purine and uridine residues, which critically contributes to the supply of catabolic uridine and the generation of purine-2′,3′-cyclophosphate-terminated oligoribonucleotides. Thus-generated molecules constitute agonistic ligands for the first and second binding pocket of TLR8. Together, these results establish the identity and origin of the RNA-derived molecular pattern sensed by TLR8.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
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Institute for Chemical Epigenetics Munich (ICEM)
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Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
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LMU Munich
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LMU Munich
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LMU Munich
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