Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.
Predictable suppression of gene expression by 5'-UTR-based RNA quadruplexes.
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DOI：
10.1093/nar/gkp696
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发表时间：
2009-11
影响因子：
14.9
通讯作者：
Hartig JS
中科院分区：
文献类型：
--
作者：
Halder K;Wieland M;Hartig JS
四链 DNA 和 RNA 四链体或 G4 基序是推测在体内形成的非 B DNA 构象，尽管只有很少的明确证据被报道。利用生物信息学，已经证明了关键启动子区域内假定的 DNA G-四链体的存在，并怀疑其在转录中的调节作用。然而，在基因组 DNA 中，互补链的存在会干扰形成四链体基序的可能性。相反，RNA G4 基序没有这样的限制，因此怀疑对基因表达的强烈干扰。然而，实验证据却很少。在这里，我们展示了多种哺乳动物细胞系中 5'-UTR 中合成四链体序列的明确结构-功能关系。我们在翻译水平上建立了这些基序对基因表达的普遍“翻译抑制”效应，并首次表明诸如环长度和“GGG”重复数量等特定特征进一步决定了抑制影响。此外，观察到天然存在的 RNA G4 基序对基因表达的一致且可预测的抑制，增强了这些不寻常核酸结构的功能相关性。
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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