Toll-like receptors (TLRs) can contribute to central nervous system disease pathologies via recognition of microRNAs (miRNAs); however, it remains to be determined which miRNAs are able to activate this signaling. Here we report that numerous miRNAs induced the production of tumor necrosis factor alpha in multiple myeloid cell types, including microglia, and that this effect was abolished in cells deficient in TLR7. Examination of closely related miRNAs that differed in their ability to activate TLR7 resulted in the identification of a motif (UGCUUAU) in miR-20a-5p and specific nucleotides (all the uridines and surprisingly the cytosine as well) in a key area of miR-20a-5p and miR-148b-3p that were vital for the secretion of cytokines via TLR7 stimulation. A 10-nucleotide sequence including this motif was identified to be the shortest single-stranded RNA to signal via TLR7. An miRNA containing this motif induced the secretion of multiple proinflammatory molecules, which was dependent on the phosphoinositide 3-kinase, mitogen-activated protein kinase, and nuclear factor kappa‐light‐chain‐enhancer of activated B cell signaling pathways. Wild-type mice administered miR-20a-5p, which contained this motif, demonstrated increased leukocyte migration. This effect was significantly ameliorated in TLR7-knockout mice, and mice administered miR-20b-5p, in which the motif was mutated, did not exhibit leukocyte migration. We provide a detailed analysis of miRNAs that activate endosomal TLR7 and identify key nucleotide features of a sequence motif recognized by TLR7.

Toll 样受体 (TLR) 可通过识别 microRNA (miRNA) 促成中枢神经系统疾病的病理变化；然而，仍有待确定哪些 miRNA 能够激活该信号。在这里，我们报告了许多 miRNA 在包括小胶质细胞在内的多种骨髓细胞类型中诱导肿瘤坏死因子 α 的产生，并且这种效应在缺乏 TLR7 的细胞中被消除。对激活 TLR7 能力不同的密切相关的 miRNA 的检查导致在 miR-20a-5p 和特定核苷酸（所有的尿苷和令人惊讶的胞嘧啶）中识别出 miR-20a-5p 的一个基序（UGCUUAU）。 20a-5p 和 miR-148b-3p 通过 TLR7 刺激对细胞因子的分泌至关重要。包含该基序的 10 个核苷酸序列被确定为通过 TLR7 发出信号的最短单链 RNA。含有该基序的 miRNA 诱导多种促炎分子的分泌，这依赖于磷酸肌醇 3-激酶、丝裂原活化蛋白激酶和活化 B 细胞信号通路的核因子 kappa-轻链增强剂。给予含有该基序的 miR-20a-5p 的野生型小鼠表现出增加的白细胞迁移。这种影响在 给予含有该基序的 miR-20a-5p 的野生型小鼠表现出增加的白细胞迁移。这种影响在 给予含有该基序的 miR-20a-5p 的野生型小鼠表现出增加的白细胞迁移。这种影响在TLR7敲除小鼠和施用miR-20b-5p（其中基序发生突变）的小鼠没有表现出白细胞迁移。我们提供了对激活内体 TLR7 并识别 TLR7 识别的序列基序的关键核苷酸特征的 miRNA 的详细分析。