Analysis of secondary structural elements in human microRNA hairpin precursors.
Analysis of secondary structural elements in human microRNA hairpin precursors.
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DOI：
10.1186/s12859-016-0960-6
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发表时间：
2016-03-01
影响因子：
3
通讯作者：
Disney MD
中科院分区：
文献类型：
--
作者：
Liu B;Childs-Disney JL;Znosko BM;Wang D;Fallahi M;Gallo SM;Disney MD
微小RNA（miRNAs）通过靶向互补mRNA进行破坏或翻译抑制来调节基因表达。miRNAs的异常表达与包括癌症在内的多种疾病有关，因此使其成为有趣的治疗靶点。包含miRNAs的二级结构元件的复合物可以帮助设计调节其功能的小分子。我们分析了存在于所有人类miRNA发夹前体中的二级结构元件或基序，并将其与具有已知结构的高表达人类RNA和来自各种生物体的其他RNA进行了比较。在人类miRNAs中，有3808个是独特的基序，其中许多位于加工位点。此外，我们还鉴定了miRNA中的基序，这些基序不存在于其他高表达的人类RNA中，这些RNA是小分子的理想靶点。将miRNA基序并入可免费获得的可搜索数据库中。我们还分析了每个RNA类别中最常见的凸起和内环，发现最小的环可能占上风。然而，环的分布和优选的闭合碱基对对于每个类别是独特的。总的来说，我们已经完成了对人类miRNA前体、高表达的人类RNA和来自其他生物体的RNA中发现的基序的广泛调查。有趣的是，在人类miRNA加工位点中鉴定出独特的基序，与其结合可以抑制miRNA成熟并因此抑制其功能。本文的在线版本（doi：10.1186/s12859-016-0960-6）包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) regulate gene expression by targeting complementary mRNAs for destruction or translational repression. Aberrant expression of miRNAs has been associated with various diseases including cancer, thus making them interesting therapeutic targets. The composite of secondary structural elements that comprise miRNAs could aid the design of small molecules that modulate their function. We analyzed the secondary structural elements, or motifs, present in all human miRNA hairpin precursors and compared them to highly expressed human RNAs with known structures and other RNAs from various organisms. Amongst human miRNAs, there are 3808 are unique motifs, many residing in processing sites. Further, we identified motifs in miRNAs that are not present in other highly expressed human RNAs, desirable targets for small molecules. MiRNA motifs were incorporated into a searchable database that is freely available. We also analyzed the most frequently occurring bulges and internal loops for each RNA class and found that the smallest loops possible prevail. However, the distribution of loops and the preferred closing base pairs were unique to each class. Collectively, we have completed a broad survey of motifs found in human miRNA precursors, highly expressed human RNAs, and RNAs from other organisms. Interestingly, unique motifs were identified in human miRNA processing sites, binding to which could inhibit miRNA maturation and hence function. The online version of this article (doi:10.1186/s12859-016-0960-6) contains supplementary material, which is available to authorized users.