title: An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation.
abstract: 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.
authors.affiliation: University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Sunita
authors.initials: S
authors.lastname: Kumari
authors.forename: Anthony
authors.initials: A
authors.lastname: Bugaut
authors.forename: Julian L
authors.initials: JL
authors.lastname: Huppert
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D054856:G-Quadruplexes; D015870:Gene Expression; D006147:Guanine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D006147:Guanine; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)