Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS Pathog. 2010 Jun 24;6(6):e1000967. doi: 10.1371/journal.ppat.1000967.
Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3' untranslated region (UTR). Using RNA induced silencing complex immunoprecipitation (RISC-IP) techniques we have identified multiple cellular targets for a human cytomegalovirus (HCMV) miRNA, miR-US25-1. Strikingly, this miRNA binds target sites primarily within 5'UTRs, mediating significant reduction in gene expression. Intriguingly, many of the genes targeted by miR-US25-1 are associated with cell cycle control, including cyclin E2, BRCC3, EID1, MAPRE2, and CD147, suggesting that miR-US25-1 is targeting genes within a related pathway. Deletion of miR-US25-1 from HCMV results in over expression of cyclin E2 in the context of viral infection. Our studies demonstrate that a viral miRNA mediates translational repression of multiple cellular genes by targeting mRNA 5'UTRs.
全球基因表达数据与生物信息学分析相结合，为哺乳动物 miRNA 主要通过结合 3'非翻译区（UTR）内的结合位点来调节基因表达提供了有力证据。我们使用 RNA 诱导沉默复合物免疫沉淀（RISC-IP）技术，鉴定了人类巨细胞病毒（HCMV）miRNA miR-US25-1 的多个细胞靶标。引人注目的是，这种 miRNA 主要结合 5'UTR 中的靶标位点，介导基因表达的显著降低。有趣的是，miR-US25-1 靶向的许多基因与细胞周期控制有关，包括细胞周期蛋白 E2、BRCC3、EID1、MAPRE2 和 CD147，表明 miR-US25-1 靶向的是相关途径内的基因。HCMV 中 miR-US25-1 的缺失导致病毒感染时细胞周期蛋白 E2 的过度表达。我们的研究表明，病毒 miRNA 通过靶向 mRNA 5'UTR 来调节多个细胞基因的翻译抑制。
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