Letter abstract
Nature Chemical Biology 3, 218 - 221 (2007)
Published online: 25 February 2007 | doi:10.1038/nchembio864
An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation
Sunita Kumari1, Anthony Bugaut1, Julian L Huppert2 & Shankar Balasubramanian1
Guanine-rich nucleic acid sequences can adopt noncanonical four-stranded secondary structures called guanine (G)-quadruplexes1. Bioinformatics analysis suggests that G-quadruplex motifs are prevalent in genomes2, which raises the need to elucidate their function. There is now evidence for the existence of DNA G-quadruplexes at telomeres with associated biological function3. A recent hypothesis supports the notion that gene promoter elements contain DNA G-quadruplex motifs that control gene expression at the transcriptional level4. We discovered a highly conserved, thermodynamically stable RNA G-quadruplex in the 5' untranslated region (UTR) of the gene transcript of the human NRAS proto-oncogene. Using a cell-free translation system coupled to a reporter gene assay, we have demonstrated that this NRAS RNA G-quadruplex modulates translation. This is the first example of translational repression by an RNA G-quadruplex. Bioinformatics analysis has revealed 2,922 other 5' UTR RNA G-quadruplex elements in the human genome. We propose that RNA G-quadruplexes in the 5' UTR modulate gene expression at the translational level.
- University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
- Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Correspondence to: Shankar Balasubramanian1 e-mail: sb10031@cam.ac.uk
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