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剪接位点受蛋白质无序状态的限制。

Splice junctions are constrained by protein disorder.

作者信息

Smithers Ben, Oates Matt E, Gough Julian

机构信息

Department of Computer Science, University of Bristol, Bristol, BS8 1UB, UK

Department of Computer Science, University of Bristol, Bristol, BS8 1UB, UK.

出版信息

Nucleic Acids Res. 2015 May 26;43(10):4814-22. doi: 10.1093/nar/gkv407. Epub 2015 Apr 30.

DOI:10.1093/nar/gkv407
PMID:25934802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4446445/
Abstract

We have discovered that positions of splice junctions in genes are constrained by the tolerance for disorder-promoting amino acids in the translated protein region. It is known that efficient splicing requires nucleotide bias at the splice junction; the preferred usage produces a distribution of amino acids that is disorder-promoting. We observe that efficiency of splicing, as seen in the amino-acid distribution, is not compromised to accommodate globular structure. Thus we infer that it is the positions of splice junctions in the gene that must be under constraint by the local protein environment. Examining exonic splicing enhancers found near the splice junction in the gene, reveals that these (short DNA motifs) are more prevalent in exons that encode disordered protein regions than exons encoding structured regions. Thus we also conclude that local protein features constrain efficient splicing more in structure than in disorder.

摘要

我们发现,基因中剪接位点的位置受到翻译后蛋白质区域中促进无序化氨基酸耐受性的限制。已知高效剪接需要剪接位点处的核苷酸偏好性;这种偏好性使用会产生促进无序化的氨基酸分布。我们观察到,从氨基酸分布来看,剪接效率并未因适应球状结构而受到损害。因此我们推断,基因中剪接位点的位置必定受到局部蛋白质环境的限制。检查基因中剪接位点附近发现的外显子剪接增强子,发现这些(短DNA基序)在编码无序蛋白质区域的外显子中比编码结构化区域的外显子中更普遍。因此我们还得出结论,局部蛋白质特征对高效剪接在结构方面的限制比对无序方面的限制更大。

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本文引用的文献

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Mol Biol Evol. 2015 Jul;32(7):1847-61. doi: 10.1093/molbev/msv069. Epub 2015 Mar 13.
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Intrinsically disordered proteins in cellular signalling and regulation.细胞信号转导和调控中的无规则卷曲蛋白
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Synonymous constraint elements show a tendency to encode intrinsically disordered protein segments.
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