MicroRNA-122 (miR-122) is highly expressed in hepatocytes, where it plays an important role in regulating cholesterol and fatty acid metabolism, and it is also a host factor required for hepatitis C virus replication. miR-122 is selectively stabilized by 3' adenylation mediated by the cytoplasmic poly(A) polymerase GLD-2 (also known as PAPD4 or TENT2). However, it is unclear how GLD-2 specifically stabilizes miR-122. Here, we show that QKI7 KH domain-containing RNA binding (QKI-7), one of three isoforms of the QKI proteins, which are members of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, is involved in miR-122 stabilization. QKI down-regulation specifically decreased the steady-state level of mature miR-122, but did not affect the pre-miR-122 level. We also found that QKI-7 uses its C-terminal region to interact with GLD-2 and its QUA2 domain to associate with the RNA-induced silencing complex protein Argonaute 2 (Ago2), indicating that the GLD-2-QKI-7 interaction recruits GLD-2 to Ago2. QKI-7 exhibited specific affinity to miR-122 and significantly promoted GLD-2-mediated 3' adenylation of miR-122 in vitro Taken together, our findings indicate that miR-122 binds Ago2-interacting QKI-7, which recruits GLD-2 for 3' adenylation and stabilization of miR-122.

中文翻译：

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RNA结合蛋白QKI-7募集了poly（A）聚合酶GLD-2，用于3'腺苷酸化和microRNA-122的选择性稳定化。

MicroRNA-122（miR-122）在肝细胞中高度表达，在调节胆固醇和脂肪酸代谢中起着重要作用，它也是丙型肝炎病毒复制所需的宿主因子。miR-122通过细胞质聚（A）聚合酶GLD-2（也称为PAPD4或TENT2）介导的3'腺苷酸选择性稳定。但是，尚不清楚GLD-2如何特异性稳定miR-122。在这里，我们显示包含QKI7 KH域的RNA结合（QKI-7），是QKI蛋白的三种同工型之一，它们是RNA结合蛋白的信号转导和激活RNA（STAR）家族的成员。在miR-122稳定化中。QKI下调专门降低了成熟miR-122的稳态水平，但没有影响miR-122之前的水平。我们还发现，QKI-7使用其C末端区域与GLD-2相互作用，并利用其QUA2结构域与RNA诱导的沉默复合蛋白Argonaute 2（Ago2）缔合，表明GLD-2-QKI-7相互作用将GLD-2招募到Ago2。QKI-7表现出对miR-122的特异性亲和力，并在体外显着促进GLD-2介导的miR-122的3'腺苷酸化。综上所述，我们的发现表明miR-122结合了与Ago2相互作用的QKI-7，后者募集了GLD-2用于miR-122的3'腺苷酸化和稳定化。