Help Privacy Policy Disclaimer
  Advanced SearchBrowse




Journal Article

TLR8 Is a Sensor of RNase T2 Degradation Products


Hornung,  Veit
Hornung, Veit / Molecular Mechanisms of Inflammation, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available

Greulich, W., Wagner, M., Gaidt, M. M., Stafford, C., Cheng, Y., Linder, A., et al. (2019). TLR8 Is a Sensor of RNase T2 Degradation Products. CELL, 179(6), 1264-1275.e13. doi:10.1016/j.cell.2019.11.001.

Cite as: https://hdl.handle.net/21.11116/0000-0005-6EDC-9
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.