An RNA G-quadruplex in the 5′ UTR of the NRAS proto-oncogene modulates translation
By A. Bugaut, Julian Leon Huppert, Shankar Balasubramanian. Nature Chemical Biology, 2007
737 citations recorded by the source corpus.
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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0083c14e74a5e1db175b13726e50dbcc15243b28
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In Molecular Biology
- Shankar Balasubramanian
- Stephen Neidle
- Dinshaw J. Patel
- A. Phan
- V. Kuryavyi
- A. Bugaut
- L. Hurley
- R. Gray
Citations in the corpus
- Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? (2011, background): “Further creddence has been lent to the strategy of targeting this class of nucleic acid structures by the more recent identificatio”
- Stability and kinetics of G-quadruplex structures (2008, background): “Equation (16) is a Hill equation and will show positive binding cooperativity of L at a fixed temperature.”
- Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics (2007, methodology): “The measured tm was 638C in 1mM K cation, and the stabilization decreased in the order K>Na>Li (196).”
- 5′-UTR RNA G-quadruplexes: translation regulation and targeting (2012, background): “The special structural features of G-quadruplexes and the discovery of RNA G-quadruplex-forming-sequence in the 50-UTRs of numerous genes, including several proto-oncogenes, led us to propose that such RNA motifs could be suitable targets for small molecules (73).”