Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.
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.
Halder
Kangkan
K
Department of Chemistry, Konstanz Research School Chemical Biology and Zukunftskolleg, University of Konstanz, Universitätsstr 10, 78457 Konstanz, Germany.
Wieland
Markus
M
Hartig
Jörg S
JS
D020121:5' Untranslated Regions; D002460:Cell Line; D054856:G-Quadruplexes; D015870:Gene Expression; D006801:Humans; D012313:RNA / Q000737:chemistry*
D020121:5' Untranslated Regions; D012313:RNA