MicroRNA与作用位点的结合具有背景依赖性
首发时间:2010-03-04
摘要:MicroRNA作用位点预测是microRNA研究中十分重要的内容。目前大多数的microRNA作用位点预测方法主要基于“种子”序列互补和物种间的保守性来进行预测。而新近某些研究表明,某些背景因素,如:作用位点周围序列、mRNA自身折叠、作用位点在3’UTR区域上的位置以及同microRNA结合形成复合物的蛋白性质等都有可能对microRNA同作用位点的结合产生影响,而现有的预测方法很少考虑这类因素的影响。在本研究中,我们提出了一种基于机器学习算法的作用位点预测方法,该方法不仅考虑了多种背景因素的影响,而且由于在预测过程中不依赖于“种子”序列的互补性以及物种间的保守性,因而对于现有方法较难预测的3’端补充型作用位点和物种间不保守的作用位点也可以进行较好地预测。最后,我们系统地对各种影响结合的因素进行了研究,发现:除“种子”序列的结合之外,与“种子”序列相邻的一段结合区域的结合对结合的有效性也会产生影响;作用位点周围的AU、UA二联核苷酸对出现频率对结合的有效性会有影响;mRNA自身折叠对分子结合也会产生影响;有效结合位点往往分布在3’UTR区域前端。
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Research on the Context Dependency of MicroRNA-target Interaction
Abstract:MicroRNA target prediction is an important work in microRNA research field. Traditional prediction methods are mainly based on “seed” sequence complementarity and evolutionary conservation among species. Several recent researches suggested that some context factors such as sequences flanking target site, secondary structures of mRNA, positions of target site and proteins wrapping microRNA may all influence microRNA-target interaction, but traditional prediction methods haven’t taken these factors into account. In our research, we proposed a new prediction method based on machine-learning algorithm. This method not only considers various context factors, but also can find 3’-complementary sites and non-conservation sites preferably because its prediction didn’t depend on “seed” sequence complementarity and evolutionary conservation. And these target sites can’t be predicted by traditional methods generally. Finally, we investigated various factors which may influence microRNA-target interaction. Besides “seed” sequence complementarity, we found that the base-pairings of a sequence region bordered upon “seed” region, frequency of AU, UA dinucleotide flanking target site and secondary structures of mRNA can all influence binding, in addition, effective binding sites prefer to distribute within the front of 3’UTR.
Keywords: microRNA target prediction machine-learning context dependency
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