Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.
Cellular microRNA let-7c inhibits M1 protein expression of the H1N1 influenza A virus in infected human lung epithelial cells.
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DOI：
10.1111/j.1582-4934.2012.01572.x
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发表时间：
2012-10
影响因子：
5.3
通讯作者：
Wang SQ
中科院分区：
文献类型：
--
作者：
Ma YJ;Yang J;Fan XL;Zhao HB;Hu W;Li ZP;Yu GC;Ding XR;Wang JZ;Bo XC;Zheng XF;Zhou Z;Wang SQ
流感病毒（IV）在宿主细胞内触发一系列信号事件并诱导复杂的细胞反应。研究表明，宿主因子在IV复制中起重要作用。MicroRNAs （miRNAs）是一类小的非编码RNA，其靶向mrna，引发翻译抑制或RNA降解。新的研究表明，宿主来源的细胞mirna参与介导宿主- iv相互作用。使用miRNA微阵列，我们鉴定了几种miRNA在iv感染的人肺上皮细胞（A549）中异常表达。具体来说，miR-let-7c在iv感染的A549细胞中被高度上调。PITA和miRanda数据库筛选表明，let-7c种子序列与病毒基因M1 (+) cRNA的3′非翻译区（UTR）完全匹配，但与PB2和PA不匹配。通过荧光素酶报告系统检测，let-7c直接靶向M1 (+) cRNA的3 ' -UTR，而不是PB2和PA。为了实验鉴定细胞let-7c的功能，将前体let-7c转染到A549细胞中。Let-7c在（+）cRNA和蛋白水平上下调IV M1的表达。此外，转染let-7c抑制剂可增强M1的表达。因此，let-7c可能通过降解M1 (+) cRNA来减少IV复制。这是首次报道细胞miRNA通过匹配病毒cRNA的3 ' -UTR，通过病毒基因（+）cRNA的降解来调控IV复制。这些发现表明，除了已知的细胞功能外，let-7c还在保护宿主细胞免受病毒侵害方面发挥作用。
The influenza virus (IV) triggers a series of signalling events inside host cells and induces complex cellular responses. Studies have suggested that host factors play an essential role in IV replication. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that target mRNAs, triggering either translation repression or RNA degradation. Emerging research suggests that host-derived cellular miRNAs are involved in mediating the host–IV interaction. Using miRNA microarrays, we identified several miRNAs aberrantly expressed in IV-infected human lung epithelial cells (A549). Specifically, miR-let-7c was highly up-regulated in IV-infected A549 cells. PITA and miRanda database screening indicated that the let-7c seed sequence is a perfect complementary sequence match to the 3′ untranslated region (UTR) of viral gene M1 (+) cRNA, but not to PB2 and PA. As detected by a luciferase reporter system, let-7c directly targeted the 3′-UTR of M1 (+) cRNA, but not PB2 and PA. To experimentally identify the function of cellular let-7c, precursor let-7c was transfected into A549 cells. Let-7c down-regulated IV M1 expression at both the (+) cRNA and protein levels. Furthermore, transfection with a let-7c inhibitor enhanced the expression of M1. Therefore, let-7c may reduce IV replication by degrading M1 (+) cRNA. This is the first report indicating that cellular miRNA regulates IV replication through the degradation of viral gene (+) cRNA by matching the 3′-UTR of the viral cRNA. These findings suggest that let-7c plays a role in protecting host cells from the virus in addition to its known cellular functions.
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