SSMART: sequence-structure motif identification for RNA-binding proteins

SSMART: sequence-structure motif identification for RNA-binding proteins
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DOI:
10.1093/bioinformatics/bty404
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发表时间:
2018-12-01
期刊:
影响因子:
5.8
通讯作者:
Ohler, Uwe
Ohler, Uwe
中科院分区:
生物学3区
文献类型:
--
作者:
Munteanu, Aline;Mukherjee, Neelanjan;Ohler, Uwe

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RNA结合蛋白(RBP)调节RNA代谢和功能的各个方面。真核生物基因组中编码有数百种RBP,每种RBP都通过RNA序列和结构特性的特定混合物识别其RNA靶标。然而,对于大多数RBP,只有一个主要的序列基序已被确定,而结合位点的结构是uncharacterized.Results:我们开发了SSMART,RNA基序发现者,同时建模的主要序列和结构特性的RNA靶位点。序列结构基序被表示为在简并字母表上的共识字符串,扩展了核苷酸的IUPAC代码以考虑二级结构偏好。对合成数据的评估表明,SSMART能够恢复植入3 'UTR样序列的序列和结构基序,用于不同程度的结构化/非结构化结合位点。此外,我们成功地将SSMART用于高通量的体内和体外数据,表明我们不仅恢复了已知的序列基序,而且还深入了解了RBP的结构偏好。
Motivation: RNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized.Results: We developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3'UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP.