MicroRNA-373 induces expression of genes with complementary promoter sequences

MicroRNA-373 induces expression of genes with complementary promoter sequences

February 5, 2008 | Robert F. Place*, Long-Cheng Li*, Deepa Pookot*, Emily J. Noonan*, and Rajvir Dahiya**††
The study by Place et al. investigates the novel function of microRNA-373 (miR-373) in gene expression induction. By analyzing gene promoters, they identified a putative miR-373 target site in the promoter of E-cadherin. Transfection of miR-373 and its precursor hairpin RNA (pre-miR-373) into PC-3 cells significantly induced E-cadherin expression. Knockdown experiments confirmed that this induction required the miRNA maturation protein Dicer. Additionally, cold-shock domain-containing protein C2 (CSDC2), which also contains a putative miR-373 target site, was induced by miR-373. Enrichment of RNA polymerase II at the promoters of E-cadherin and CSDC2 was observed after miR-373 transfection. Mismatch mutations to miR-373 indicated that the induction was sequence-specific. Transfection of promoter-specific double-stranded RNAs (dsRNAs) revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. These findings suggest that miR-373 can induce gene expression by targeting complementary sequences in gene promoters, providing a new mode of miRNA regulation.The study by Place et al. investigates the novel function of microRNA-373 (miR-373) in gene expression induction. By analyzing gene promoters, they identified a putative miR-373 target site in the promoter of E-cadherin. Transfection of miR-373 and its precursor hairpin RNA (pre-miR-373) into PC-3 cells significantly induced E-cadherin expression. Knockdown experiments confirmed that this induction required the miRNA maturation protein Dicer. Additionally, cold-shock domain-containing protein C2 (CSDC2), which also contains a putative miR-373 target site, was induced by miR-373. Enrichment of RNA polymerase II at the promoters of E-cadherin and CSDC2 was observed after miR-373 transfection. Mismatch mutations to miR-373 indicated that the induction was sequence-specific. Transfection of promoter-specific double-stranded RNAs (dsRNAs) revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. These findings suggest that miR-373 can induce gene expression by targeting complementary sequences in gene promoters, providing a new mode of miRNA regulation.
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[slides and audio] MicroRNA-373 induces expression of genes with complementary promoter sequences