MicroRNA-373 induces expression of genes with complementary promoter sequences.
Recent studies have shown that microRNA (miRNA) regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report new evidence in which miRNA may also function to induce gene expression. By scanning gene promoters in silico for sequences complementary to known miRNAs, we 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 readily induced E-cadherin expression. Knockdown experiments confirmed that induction of E-cadherin by pre-miR-373 required the miRNA maturation protein Dicer. Further analysis revealed that cold-shock domain-containing protein C2 (CSDC2), which possesses a putative miR-373 target site within its promoter, was also readily induced in response to miR-373 and pre-miR-373. Furthermore, enrichment of RNA polymerase II was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection. Mismatch mutations to miR-373 indicated that gene induction was specific to the miR-373 sequence. Transfection of promoter-specific dsRNAs revealed that the concurrent induction of E-cadherin and CSDC2 by miR-373 required the miRNA target sites in both promoters. In conclusion, we have identified a miRNA that targets promoter sequences and induces gene expression. These findings reveal a new mode by which miRNAs may regulate gene expression.
Place
Robert F
RF
Department of Urology, Veterans Affairs Medical Center and University of California, San Francisco, CA 94121, USA. place.robert@gmail.com
Li
Long-Cheng
LC
Pookot
Deepa
D
Noonan
Emily J
EJ
Dahiya
Rajvir
R
D020137:Base Pair Mismatch; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012319:RNA Polymerase II / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D043244:Ribonuclease III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
C527115:CSDC2 protein, human; D015820:Cadherins; C527114:MIRN373 microRNA, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D012319:RNA Polymerase II; D043244:Ribonuclease III