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TLR8 Is a Sensor of RNase T2 Degradation Products.
Cell ( IF 45.5 ) Pub Date : 2019-11-27 , DOI: 10.1016/j.cell.2019.11.001 Wilhelm Greulich 1 , Mirko Wagner 2 , Moritz M Gaidt 3 , Che Stafford 1 , Yiming Cheng 1 , Andreas Linder 4 , Thomas Carell 5 , Veit Hornung 6
Cell ( IF 45.5 ) Pub Date : 2019-11-27 , DOI: 10.1016/j.cell.2019.11.001 Wilhelm Greulich 1 , Mirko Wagner 2 , Moritz M Gaidt 3 , Che Stafford 1 , Yiming Cheng 1 , Andreas Linder 4 , Thomas Carell 5 , Veit Hornung 6
Affiliation
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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.
中文翻译：
TLR8是RNase T2降解产物的传感器。
TLR8是人类髓样区室中表达最高的模式识别受体之一，但对其作用方式知之甚少。TLR8接合两个不同的配体结合位点以检测RNA降解产物，尽管目前尚不清楚在复杂RNA分子检测中纤维素中这些配体如何形成。在这里，我们确定了溶酶体内核糖核酸酶RNase T2为TLR8依赖性RNA识别的非冗余上游成分。RNase T2活性是使TLR8可以检测到的复杂单链外源RNA分子所必需的。这是由于RNase T2在嘌呤和尿苷残基之间优先切割单链RNA分子，这对分解代谢性尿苷的供应和嘌呤2'，3'的产生至关重要。-环磷酸酯封端的寡核糖核苷酸。如此产生的分子构成TLR8的第一和第二结合口袋的激动性配体。总之，这些结果确定了由TLR8感知的RNA衍生分子模式的身份和起源。
更新日期：2019-11-28
中文翻译：
TLR8是RNase T2降解产物的传感器。
TLR8是人类髓样区室中表达最高的模式识别受体之一，但对其作用方式知之甚少。TLR8接合两个不同的配体结合位点以检测RNA降解产物，尽管目前尚不清楚在复杂RNA分子检测中纤维素中这些配体如何形成。在这里，我们确定了溶酶体内核糖核酸酶RNase T2为TLR8依赖性RNA识别的非冗余上游成分。RNase T2活性是使TLR8可以检测到的复杂单链外源RNA分子所必需的。这是由于RNase T2在嘌呤和尿苷残基之间优先切割单链RNA分子，这对分解代谢性尿苷的供应和嘌呤2'，3'的产生至关重要。-环磷酸酯封端的寡核糖核苷酸。如此产生的分子构成TLR8的第一和第二结合口袋的激动性配体。总之，这些结果确定了由TLR8感知的RNA衍生分子模式的身份和起源。
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