Using RNA secondary structures to guide sequence motif finding towards single-stranded regions.

Using RNA secondary structures to guide sequence motif finding towards single-stranded regions.
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使用RNA二级结构指导序列基序发现对单链区域。

DOI:
10.1093/nar/gkl544
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发表时间:
2006
影响因子:
14.9
通讯作者:
Backofen R
Backofen R
中科院分区:
生物学2区
文献类型:
--
作者:
Hiller M;Pudimat R;Busch A;Backofen R

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RNA结合蛋白以序列特异性的方式识别RNA靶标。除序列外,结合位点的二级结构上下文也影响结合亲和力。结合位点通常位于单链RNA区域,研究表明,结合基序在双链中的隔离取消了蛋白质的结合。因此,在搜索蛋白质的结合基序时,希望包括有关RNA二级结构的知识。我们提出了一种在一组RNA序列中搜索序列基序并同时整合二级结构信息的方法MEMERIS。为了从特定的结构元素中抽象出来,我们预先计算出测量RNA序列所有子串的单链的位置特定值。这些值被用作关于主题开始的先验知识来指导主题搜索。用人工和生物数据进行的广泛测试表明,即使存在位于双链部分的更强的基序,MEMERIS也能够识别单链区域的基序。在生物数据集中发现的基序大多与已知的蛋白质结合位点相吻合。该算法可用于在SELEX或其他生物序列数据中寻找单链RNA结合蛋白的结合基序。
RNA binding proteins recognize RNA targets in a sequence specific manner. Apart from the sequence, the secondary structure context of the binding site also affects the binding affinity. Binding sites are often located in single-stranded RNA regions and it was shown that the sequestration of a binding motif in a double-strand abolishes protein binding. Thus, it is desirable to include knowledge about RNA secondary structures when searching for the binding motif of a protein. We present the approach MEMERIS for searching sequence motifs in a set of RNA sequences and simultaneously integrating information about secondary structures. To abstract from specific structural elements, we precompute position-specific values measuring the single-strandedness of all substrings of an RNA sequence. These values are used as prior knowledge about the motif starts to guide the motif search. Extensive tests with artificial and biological data demonstrate that MEMERIS is able to identify motifs in single-stranded regions even if a stronger motif located in double-strand parts exists. The discovered motif occurrences in biological datasets mostly coincide with known protein-binding sites. This algorithm can be used for finding the binding motif of single-stranded RNA-binding proteins in SELEX or other biological sequence data.
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