Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif.

نویسندگان

  • Amit Arora
  • Mariola Dutkiewicz
  • Vinod Scaria
  • Manoj Hariharan
  • Souvik Maiti
  • Jens Kurreck
چکیده

Guanine-rich sequences can adopt intramolecular four-stranded structures, called G-quadruplexes. These motifs have been intensively investigated on the DNA level, but their overall biological relevance remains elusive. Only recently has research concerning the function of G-quadruplexes in RNAs commenced. Here, we demonstrate for the first time, that an RNA G-quadruplex structure inhibits translation in vivo in eukaryotic cells. We investigated the function of a highly conserved, thermodynamically stable RNA G-quadruplex in the 5'-UTR of the mRNA of the human Zic-1 zinc-finger protein. Using dual luciferase reporter assay, we demonstrate that the Zic-1 RNA G-quadruplex represses protein synthesis inside eukaryotic cells. Quantitative RT-PCR assays confirmed that the reduction of protein synthesis is due to regulation of the translation process and not a consequence of reduced transcription. Western blot analysis revealed that expression of Zic-1 is strongly reduced by a 73 nucleotides-long fragment of the UTR containing the G-quadruplex motif. These structures might add to the more recently discovered elements in untranslated regions of mRNAs that regulate their translation.

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عنوان ژورنال:
  • RNA

دوره 14 7  شماره 

صفحات  -

تاریخ انتشار 2008