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Nat Chem Biol.
2007 Apr;3(4):218-21. Epub 2007 Feb 25.
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Comment in:
Nat Chem Biol. 2007 Apr;3(4):203-4.
An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation.
Kumari S
,
Bugaut A
,
Huppert JL
,
Balasubramanian S
.
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
Guanine-rich nucleic acid sequences can adopt noncanonical four-stranded secondary structures called guanine (G)-quadruplexes. Bioinformatics analysis suggests that G-quadruplex motifs are prevalent in genomes, which raises the need to elucidate their function. There is now evidence for the existence of DNA G-quadruplexes at telomeres with associated biological function. A recent hypothesis supports the notion that gene promoter elements contain DNA G-quadruplex motifs that control gene expression at the transcriptional level. 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.
Publication Types:
Research Support, Non-U.S. Gov't
PMID: 17322877 [PubMed - indexed for MEDLINE]
PMCID: PMC2206252
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