HuR recruits let-7/RISC to repress c-Myc expression
- Hyeon Ho Kim,2,
- Yuki Kuwano,
- Subramanya Srikantan,
- Eun Kyung Lee,
- Jennifer L. Martindale and
- Myriam Gorospe,1
- Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA
Abstract
RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with the c-Myc 3′ untranslated region (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc expression and HuR required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3′UTR.
Keywords
Footnotes
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↵1 Corresponding authors.
E-MAIL myriam-gorospe{at}nih.gov; FAX (410) 558-8386.
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↵2 E-MAIL kimhye{at}grc.nia.nih.gov; FAX (410) 558-8386.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1812509.
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Supplemental material is available at http://www.genesdev.org.
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- Received April 16, 2009.
- Accepted June 5, 2009.
