Dataset Information

Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.

ABSTRACT: 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.

SUBMITTER: Halder K

PROVIDER: S-EPMC2777418 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.

Halder Kangkan K Wieland Markus M Hartig Jörg S JS

Nucleic acids research 20090909 20

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 hav ...[more]

PMID: 19740765

Similar Datasets

Project description:Asymptomatic bacteriuria (ABU) is a bacterial carrier state in the urinary tract that resembles commensalism at other mucosal sites. ABU strains often lack the virulence factors that characterize uropathogenic Escherichia coli (E. coli) strains and therefore elicit weak innate immune responses in the urinary tract. In addition, ABU strains are active modifiers of the host environment, which they influence by suppressing RNA polymerase II (Pol II)-dependent host gene expression. In patients inoculated with the ABU strain E. coli 83972, gene expression was markedly reduced after 24 h (>60% of all regulated genes). Specific repressors and activators of Pol II-dependent transcription were modified, and Pol II Serine 2 phosphorylation was significantly inhibited, indicating reduced activity of the polymerase. This active inhibition included disease-associated innate immune response pathways, defined by TLR4, IRF-3 and IRF-7, suggesting that ABU strains persist in human hosts by active suppression of the antibacterial defense. In a search for the mechanism of inhibition, we compared the whole genome sequences of E. coli 83972 and the uropathogenic strain E. coli CFT073. In addition to the known loss of virulence genes, we observed that the ABU strain has acquired several phages and identified the lytic Prophage 3 as a candidate Pol II inhibitor. Intact phage particles were released by ABU during in vitro growth in human urine. To address if Prophage 3 affects Pol II activity, we constructed a Prophage 3 negative deletion mutant in E. coli 83972 and compared the effect on Pol II phosphorylation between the mutant and the E. coli 83972 wild type (WT) strains. No difference was detected, suggesting that the Pol II inhibitor is not encoded by the phage. The review summarizes the evidence that the ABU strain E. coli 83972 modifies host gene expression by inhibition of Pol II phosphorylation, and discusses the ability of ABU strains to actively create an environment that enhances their persistence.

Project description:Contextual information triggers predictions about the content ("what") of environmental stimuli to update an internal generative model of the surrounding world. However, visual information dynamically changes across time, and temporal predictability ("when") may influence the impact of internal predictions on visual processing. In this magnetoencephalography (MEG) study, we investigated how processing feature specific information ("what") is affected by temporal predictability ("when"). Participants (N = 16) were presented with four consecutive Gabor patches (entrainers) with constant spatial frequency but with variable orientation and temporal onset. A fifth target Gabor was presented after a longer delay and with higher or lower spatial frequency that participants had to judge. We compared the neural responses to entrainers where the Gabor orientation could, or could not be temporally predicted along the entrainer sequence, and with inter-entrainer timing that was constant (predictable), or variable (unpredictable). We observed suppression of evoked neural responses in the visual cortex for predictable stimuli. Interestingly, we found that temporal uncertainty increased expectation suppression. This suggests that in temporally uncertain scenarios the neurocognitive system invests less resources in integrating bottom-up information. Multivariate pattern analysis showed that predictable visual features could be decoded from neural responses. Temporal uncertainty did not affect decoding accuracy for early visual responses, with the feature specificity of early visual neural activity preserved across conditions. However, decoding accuracy was less sustained over time for temporally jittered than for isochronous predictable visual stimuli. These findings converge to suggest that the cognitive system processes visual features of temporally predictable stimuli in higher detail, while processing temporally uncertain stimuli may rely more heavily on abstract internal expectations.

Dataset Information

Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.

Publications

Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets