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HuR recruits let-7/RISC to repress c-Myc expression
Hyeon Ho Kim1, Yuki Kuwano, Subramanya Srikantan
1Laboratory of Cellular and Molecular Biology, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA. kimhye@grc.nia.nih.gov
Genes & Development
|July 4, 2009
Summary
The RNA-binding protein HuR and microRNA let-7 cooperatively repress c-Myc expression. This interdependent mechanism involves HuR recruiting let-7 to the c-Myc 3' untranslated region, inhibiting translation.
Area of Science:
- Molecular Biology
- Gene Regulation
- Post-transcriptional Control
Background:
- RNA-binding proteins (RBPs) and microRNAs (miRNAs) are key regulators of gene expression.
- Post-transcriptional regulation significantly impacts cellular processes and disease development.
Purpose of the Study:
- To investigate the regulatory relationship between HuR, let-7, and c-Myc expression.
- To elucidate the mechanism by which HuR and let-7 interact to control c-Myc translation.
Main Methods:
- Analysis of HuR and let-7 binding to the c-Myc 3' untranslated region (UTR).
- Manipulation of HuR and let-7 levels to assess their impact on c-Myc expression.
- Investigation of the interdependence between HuR and let-7 in regulating c-Myc.
Main Results:
- HuR directly associates with the c-Myc 3'UTR near a let-7 binding site, repressing c-Myc translation.
- Reduced levels of either HuR or let-7 alleviate the translational repression of c-Myc.
- HuR and let-7 exhibit an interdependent mechanism, each requiring the other for c-Myc repression.
Conclusions:
- HuR and let-7 function in a coordinated manner to inhibit c-Myc expression.
- HuR facilitates c-Myc repression by recruiting let-7-loaded RISC to the c-Myc 3'UTR.
- This study reveals a novel regulatory paradigm for c-Myc expression involving RBP-miRNA cooperation.
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