Increasing evidence suggests mammalian Argonaute (Ago) proteins partition into distinct complexes within cells, but there is still little biochemical or functional understanding of the miRNAs differentially associated with these complexes. In naïve T cells, Ago2 is found almost exclusively in low molecular weight (LMW) complexes which are associated with miRNAs but not their target mRNAs. Upon T-cell activation, a proportion of these Ago2 complexes move into a newly formed high molecular weight (HMW) RNA-induced silencing complex (RISC), which is characterized by the presence of the GW182 protein that mediates translational repression. Here, we demonstrate distinct partitioning of miRNAs and isomiRs in LMW versus HMW RISCs upon antigen-mediated activation of CD8⁺ T cells. We identify miR-7 as highly enriched in HMW RISC and demonstrate that miR-7 inhibition leads to increased production of IL-2 and up-regulation of the IL-2 receptor, the transferrin receptor, CD71 and the amino acid transporter, CD98. Our data support a model where recruitment of miR-7 to HMW RISC restrains IL-2 signaling and the metabolic processes regulated by IL-2.

中文翻译：

---

激活后，miR-7 被招募到 CD8+ T 细胞中高分子量 RNA 诱导的沉默复合物中，并抑制 IL-2 信号传导

越来越多的证据表明哺乳动物 Argonaute (Ago) 蛋白在细胞内划分成不同的复合物，但对与这些复合物差异相关的 miRNA 的生化或功能了解仍然很少。在初始 T 细胞中，Ago2 几乎只存在于低分子量 (LMW) 复合物中，该复合物与 miRNA 相关，但与其靶标 mRNA 无关。 T 细胞激活后，这些 Ago2 复合物的一部分会进入新形成的高分子量 (HMW) RNA 诱导沉默复合物 (RISC)，其特征是存在介导翻译抑制的 GW182 蛋白。在这里，我们证明了在抗原介导的 CD8⁺ T 细胞激活后，LMW 与 HMW RISC 中 miRNA 和 isomiR 的不同分配。我们鉴定出 miR-7 在 HMW RISC 中高度富集，并证明 miR-7 抑制导致 IL-2 产生增加以及 IL-2 受体、转铁蛋白受体、CD71 和氨基酸转运蛋白 CD98 的上调。我们的数据支持这样一个模型：将 miR-7 招募到 HMW RISC 会抑制 IL-2 信号传导和 IL-2 调节的代谢过程。