a viral microrna down-regulates multiple cell cycle genes through mrna 5′utrs微rna病毒下调多种细胞周期基因通过信使rna 5u2032utr.pdfVIP

A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 59UTRs 1 ¤ 1. 1. 3 2,3 Finn Grey * , Rebecca Tirabassi , Heather Meyers , Guanming Wu , Shannon McWeeney , Lauren Hook1, Jay A. Nelson1 1Vaccine and Gene Therapy Institute, Oregon Health Science University, Portland, Oregon, United States of America, 2 Knight Cancer Institute, Oregon Health Science University, Portland, Oregon, United States of America, 3 OCTRI, Oregon Health Science University, Portland, Oregon, United States of America Abstract 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 39 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 59UTRs, 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 59UTRs. Citation: Grey F, Tirabassi R, Meyers H, Wu G, McWeeney S, et al. (2010) A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 59UTRs. PLoS Pathog 6(6): e10