Evidence of direct complementary interactions between messenger RNAs and their cognate proteins.
Evidence of direct complementary interactions between messenger RNAs and their cognate proteins.
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DOI：
10.1093/nar/gkt618
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发表时间：
2013-10
影响因子：
14.9
通讯作者：
Zagrovic B
中科院分区：
文献类型：
--
作者：
Polyansky AA;Zagrovic B
最近，已经报道了许多已知的RNA结合蛋白与信使RNA（mRNA）相互作用的能力，但令人惊讶的是，也报道了不具有可识别的RNA结合结构域的不同蛋白，包括几种转录因子和代谢酶。此外，已经检测到多种蛋白质与同源mRNA的直接结合，从而产生了寻找这种相互作用背后的功能意义和基本物理化学原理的强大动力。在这里，我们通过分析已知的蛋白质-RNA复合物的3D结构中的结合界面来获得氨基酸和RNA碱基之间的相互作用偏好。通过将该工具应用于人类蛋白质组，我们揭示了mRNA序列的组成与它们编码的蛋白质序列的碱基结合偏好之间的统计学显著匹配。例如，mRNA序列的嘌呤密度分布以定量准确度反映了同源蛋白质序列的鸟嘌呤亲和力分布（整个人类蛋白质组的皮尔逊相关系数中位数R =-0.80）。值得注意的是，仅在腺嘌呤的情况下观察到统计学显著的反匹配。我们的研究结果为遗传密码的立体化学基础提供了强有力的证据，并表明mRNA和同源蛋白质通常可以直接相互互补和关联，特别是如果非结构化。
Recently, the ability to interact with messenger RNA (mRNA) has been reported for a number of known RNA-binding proteins, but surprisingly also for different proteins without recognizable RNA binding domains including several transcription factors and metabolic enzymes. Moreover, direct binding to cognate mRNAs has been detected for multiple proteins, thus creating a strong impetus to search for functional significance and basic physico-chemical principles behind such interactions. Here, we derive interaction preferences between amino acids and RNA bases by analyzing binding interfaces in the known 3D structures of protein–RNA complexes. By applying this tool to human proteome, we reveal statistically significant matching between the composition of mRNA sequences and base-binding preferences of protein sequences they code for. For example, purine density profiles of mRNA sequences mirror guanine affinity profiles of cognate protein sequences with quantitative accuracy (median Pearson correlation coefficient R = −0.80 across the entire human proteome). Notably, statistically significant anti-matching is seen only in the case of adenine. Our results provide strong evidence for the stereo-chemical foundation of the genetic code and suggest that mRNAs and cognate proteins may in general be directly complementary to each other and associate, especially if unstructured.
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影响因子：
14.9
作者：
Anders G;Mackowiak SD;Jens M;Maaskola J;Kuntzagk A;Rajewsky N;Landthaler M;Dieterich C
通讯作者：
Dieterich C
影响因子：
14.9
作者：
Iwakiri J;Tateishi H;Chakraborty A;Patil P;Kenmochi N
通讯作者：
Kenmochi N
影响因子：
64.8
作者：
BRENNER, S;MESELSON, M;JACOB, F
通讯作者：
JACOB, F
影响因子：
14.9
作者：
Hoffman, MM;Khrapov, MA;Ellington, AD
通讯作者：
Ellington, AD
影响因子：
5.6
作者：
Gupta, Aditi;Gribskov, Michael
通讯作者：
Gribskov, Michael