A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5′UTRs

PLoS Pathogens

Shannon McWeeney¹  Guanming Wu²  Lauren Hook²  Heather Meyers³  Finn Grey³  Rebecca Tirabassi³  Jay A. Nelson³ 

[1] Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, United States of America;OCTRI, Oregon Health & Science University, Portland, Oregon, United States of America;Vaccine and Gene Therapy Institute, Oregon Health & Science University, Portland, Oregon, United States of America

关键词: MicroRNAs;    Cyclins;    Immunoprecipitation;    Gene expression;    Fibroblasts;    Cell cycle;    cell division;    Luciferase;    Gene regulation;   

DOI  :  10.1371/journal.ppat.1000967

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY