An RNA G-quadruplex in the 5' UTR of the NRAS proto-oncogene modulates translation

Nat Chem Biol. 2007 Apr;3(4):218-21. doi: 10.1038/nchembio864. Epub 2007 Feb 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics*
  • Animals
  • Base Sequence
  • DNA / genetics*
  • G-Quadruplexes
  • Gene Expression*
  • Guanine / chemistry
  • Guanine / metabolism
  • Humans
  • Molecular Sequence Data
  • Plasmids
  • Protein Biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / biosynthesis*
  • Proto-Oncogene Proteins p21(ras) / genetics

Substances

  • 5' Untranslated Regions
  • Guanine
  • DNA
  • Proto-Oncogene Proteins p21(ras)

Associated data

  • GENBANK/AM489486
  • GENBANK/AM489487
  • GENBANK/AM489488