Institute of Information Science, Academia Sinica, Taipei, 115, Taiwan, Bioinformatics Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 115, Taiwan and Institute of Biomedical Informatics, National Yang-Ming University, Taipei, 112, Taiwan.
Nucleic Acids Res. 2014 Jan;42(2):739-47. doi: 10.1093/nar/gkt939. Epub 2013 Oct 22.
Non-B DNA structures are abundant in the genome and are often associated with critical biological processes, including gene regulation, chromosome rearrangement and genome stabilization. In particular, G-quadruplex (G4) may affect alternative splicing based on its ability to impede the activity of RNA polymerase II. However, the specific role of non-B DNA structures in splicing regulation still awaits investigation. Here, we provide a genome-wide and cross-species investigation of the associations between five non-B DNA structures and exon skipping. Our results indicate a statistically significant correlation of each examined non-B DNA structures with exon skipping in both human and mouse. We further show that the contributions of non-B DNA structures to exon skipping are influenced by the occurring region. These correlations and contributions are also significantly different in human and mouse. Finally, we detailed the effects of G4 by showing that occurring on the template strand and the length of G-run, which is highly related to the stability of a G4 structure, are significantly correlated with exon skipping activity. We thus show that, in addition to the well-known effects of RNA and protein structure, the relative positional arrangement of intronic non-B DNA structures may also impact exon skipping.
非 B 型 DNA 结构在基因组中大量存在，通常与关键的生物过程相关，包括基因调控、染色体重排和基因组稳定。特别是，G-四链体（G4）可以通过阻碍 RNA 聚合酶 II 的活性来影响选择性剪接。然而，非 B 型 DNA 结构在剪接调控中的具体作用仍有待研究。在这里，我们进行了一项全基因组和跨物种的研究，探讨了五种非 B 型 DNA 结构与外显子跳跃之间的关联。我们的结果表明，在人类和小鼠中，每种被检测到的非 B 型 DNA 结构与外显子跳跃都存在统计学上显著的相关性。我们进一步表明，非 B 型 DNA 结构对外显子跳跃的贡献受到发生区域的影响。这些相关性和贡献在人类和小鼠中也存在显著差异。最后，我们通过展示模板链上 G4 的发生以及与 G4 结构稳定性高度相关的 G-串联长度，详细说明了 G4 的作用，这与外显子跳跃活性显著相关。因此，我们表明，除了众所周知的 RNA 和蛋白质结构的影响外，内含子中非 B 型 DNA 结构的相对位置排列也可能影响外显子跳跃。
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