Intercellular miRNA exchange acts as a key mechanism to control gene expression post-transcriptionally in mammalian cells. Regulated export of repressive miRNAs allows the expression of inflammatory cytokines in activated macrophages. Intracellular trafficking of miRNAs from the endoplasmic reticulum to endosomes is a rate-determining step in the miRNA export process and plays an important role in controlling cellular miRNA levels and inflammatory processes in macrophages. We have identified the SNARE protein Syntaxin 5 (STX5) to show a synchronized expression pattern with miRNA activity loss in activated mammalian macrophage cells. STX5 is both necessary and sufficient for macrophage activation and clearance of the intracellular pathogen from infected macrophages. Exploring the mechanism of how STX5 acts as an immunostimulant, we have identified the RNA-binding property of this SNARE protein that binds specific miRNAs and facilitates their accumulation in endosomes in a cooperative manner with human ELAVL1 protein, Human antigen R. This activity ensures the export of miRNAs and allows the expression of miRNA-repressed cytokines. Conversely, in its dual role in miRNA export, this SNARE protein prevents lysosomal targeting of endosomes by enhancing the fusion of miRNA-loaded endosomes with the plasma membrane to ensure accelerated release of extracellular vesicles and associated miRNAs.

中文翻译：

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人类抗原 R 将 miRNA 转移至 Syntaxin 5，以协同活化巨噬细胞的 miRNA 输出

细胞间 miRNA 交换是哺乳动物细胞转录后控制基因表达的关键机制。抑制性 miRNA 的调节输出允许炎症细胞因子在活化的巨噬细胞中表达。 miRNA 从内质网到内体的细胞内运输是 miRNA 输出过程中的速率决定步骤，在控制细胞 miRNA 水平和巨噬细胞炎症过程中发挥着重要作用。我们已经鉴定出 SNARE 蛋白 Syntaxin 5 (STX5) 在活化的哺乳动物巨噬细胞中显示出与 miRNA 活性丧失同步的表达模式。 STX5 对于巨噬细胞激活和从受感染的巨噬细胞中清除细胞内病原体来说既是必要的也是充分的。在探索 STX5 如何作为免疫刺激剂发挥作用的机制中，我们已经确定了这种 SNARE 蛋白的 RNA 结合特性，它可以与特定的 miRNA 结合，并以与人类 ELAVL1 蛋白（人类抗原 R）合作的方式促进它们在内体中的积累。这种活性确保了miRNA 的输出并允许 miRNA 抑制的细胞因子的表达。相反，由于其在 miRNA 输出中的双重作用，这种 SNARE 蛋白通过增强负载 miRNA 的内涵体与质膜的融合来防止溶酶体靶向内涵体，以确保细胞外囊泡和相关 miRNA 的加速释放。