Journal
NUCLEIC ACIDS RESEARCH
Volume 37, Issue 20, Pages 6811-6817Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp696
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Funding
- Lichtenberg-Professorship by VolkswagenStiftung
- Alexander von Humboldt-Foundation fellowship
- University of Konstanz
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Four-stranded DNA and RNA quadruplexes or G4 motifs are non-B DNA conformations that are presumed to form in vivo, although only few explicit evidence has been reported. Using bioinformatics the presence of putative DNA G-quadruplexes within critical promoter regions has been demonstrated and a regulatory role in transcription has been suspected. However, in genomic DNA the presence of the complementary strand interferes with the potential to form a quadruplex motif. Contrarily RNA G4 motifs have no such limitation and consequently strong interference with gene expression is suspected. Nevertheless, experimental evidence is scarce. Here we show a well-defined structure-function relationship of synthetic quadruplex sequences in 5'-UTRs in multiple mammalian cell-lines. We establish a universal 'translational suppressor' effect of these motifs on gene expression at the translational level and show for the first time that specific features such as loop-length and the number of 'GGG'-repeats further determine the suppressive impact. Moreover, a consistent and predictable repression of gene expression is observed for naturally occurring RNA G4 motifs, augmenting the functional relevance of these unusual nucleic acid structures.
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