MicroRNA-373 Induces Expression of Genes with Complementary Promoter Sequences

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Jan 30

PMID 18227514

Citations 622

Authors

Robert F Place

Long-Cheng Li

Deepa Pookot

Emily J Noonan

Rajvir Dahiya

Affiliations

Soon will be listed here.

Abstract

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.

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References

Reinhart B, Slack F, Basson M, Pasquinelli A, Bettinger J, Rougvie A . The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000; 403(6772):901-6. DOI: 10.1038/35002607. View

He L, Thomson J, Hemann M, Hernando-Monge E, Mu D, Goodson S . A microRNA polycistron as a potential human oncogene. Nature. 2005; 435(7043):828-33. PMC: 4599349. DOI: 10.1038/nature03552. View

Elbashir S, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T . Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001; 411(6836):494-8. DOI: 10.1038/35078107. View

ODonnell K, Wentzel E, Zeller K, Dang C, Mendell J . c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005; 435(7043):839-43. DOI: 10.1038/nature03677. View

He L, Hannon G . MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522-31. DOI: 10.1038/nrg1379. View

Fire A, Xu S, Montgomery M, Kostas S, Driver S, Mello C . Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998; 391(6669):806-11. DOI: 10.1038/35888. View

Lu J, Getz G, Miska E, Alvarez-Saavedra E, Lamb J, Peck D . MicroRNA expression profiles classify human cancers. Nature. 2005; 435(7043):834-8. DOI: 10.1038/nature03702. View

Carrington J, Ambros V . Role of microRNAs in plant and animal development. Science. 2003; 301(5631):336-8. DOI: 10.1126/science.1085242. View

Ketting R, Fischer S, Bernstein E, Sijen T, Hannon G, Plasterk R . Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001; 15(20):2654-9. PMC: 312808. DOI: 10.1101/gad.927801. View

10.

Janowski B, Younger S, Hardy D, Ram R, Huffman K, Corey D . Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol. 2007; 3(3):166-73. DOI: 10.1038/nchembio860. View

11.

Enright A, John B, Gaul U, Tuschl T, Sander C, Marks D . MicroRNA targets in Drosophila. Genome Biol. 2004; 5(1):R1. PMC: 395733. DOI: 10.1186/gb-2003-5-1-r1. View

12.

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

13.

Petruk S, Sedkov Y, Riley K, Hodgson J, Schweisguth F, Hirose S . Transcription of bxd noncoding RNAs promoted by trithorax represses Ubx in cis by transcriptional interference. Cell. 2006; 127(6):1209-21. PMC: 1866366. DOI: 10.1016/j.cell.2006.10.039. View

14.

Zeng Y, Yi R, Cullen B . MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci U S A. 2003; 100(17):9779-84. PMC: 187842. DOI: 10.1073/pnas.1630797100. View

15.

Voorhoeve P, le Sage C, Schrier M, Gillis A, Stoop H, Nagel R . A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006; 124(6):1169-81. DOI: 10.1016/j.cell.2006.02.037. View

16.

Doench J, Petersen C, Sharp P . siRNAs can function as miRNAs. Genes Dev. 2003; 17(4):438-42. PMC: 195999. DOI: 10.1101/gad.1064703. View

17.

Huang H, Chien C, Jen K, Huang H . RegRNA: an integrated web server for identifying regulatory RNA motifs and elements. Nucleic Acids Res. 2006; 34(Web Server issue):W429-34. PMC: 1538840. DOI: 10.1093/nar/gkl333. View

18.

Doench J, Sharp P . Specificity of microRNA target selection in translational repression. Genes Dev. 2004; 18(5):504-11. PMC: 374233. DOI: 10.1101/gad.1184404. View

19.

Lee R, Feinbaum R, Ambros V . The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75(5):843-54. DOI: 10.1016/0092-8674(93)90529-y. View

20.

Li L, Okino S, Zhao H, Pookot D, Place R, Urakami S . Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci U S A. 2006; 103(46):17337-42. PMC: 1859931. DOI: 10.1073/pnas.0607015103. View