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  TLR8 Is a Sensor of RNase T2 Degradation Products

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.

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Genre: Journal Article

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 Creators:
Greulich, Wilhelm1, Author
Wagner, Mirko1, Author
Gaidt, Moritz M.1, Author
Stafford, Che1, Author
Cheng, Yiming1, Author
Linder, Andreas1, Author
Carell, Thomas1, Author
Hornung, Veit2, Author              
Affiliations:
1external, ou_persistent22              
2Hornung, Veit / Molecular Mechanisms of Inflammation, Max Planck Institute of Biochemistry, Max Planck Society, ou_3185245              

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Free keywords: CYSTIC LEUKOENCEPHALOPATHY; CRYSTAL-STRUCTURES; RIBONUCLEASE MC1; STRUCTURAL BASIS; RECEPTOR 7; RECOGNITION; REVEAL; INFLAMMASOME; MONOCYTES; BACTERIAL
 Abstract: 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.

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Language(s): eng - English
 Dates: 2019-11-27
 Publication Status: Published in print
 Pages: 25
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: CELL
Source Genre: Journal
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Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 179 (6) Sequence Number: - Start / End Page: 1264 - 1275.e13 Identifier: ISSN: 0092-8674