Using RNA inverse folding to identify IRES-like structural subdomains
Using RNA inverse folding to identify IRES-like structural subdomains
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DOI：
10.4161/rna.26994
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发表时间：
2013-12-01
期刊：
影响因子：
4.1
通讯作者：
Martinez-Salas, Encarnacion
中科院分区：
文献类型：
--
作者：
Dotu, Ivan;Lozano, Gloria;Martinez-Salas, Encarnacion
内部核糖体进入位点（IRES）元件控制mRNA的蛋白质合成，其在应激条件下绕过帽依赖性翻译抑制。小核糖核酸病毒IRES是顺式作用元件，组织在将核糖体募集到内部mRNA位点的模块结构域中。本研究的目的是检索短RNA序列的能力，采用RNA折叠模式与IRES结构子域保守，可能对应于RNA模块。我们已经应用了一个新的程序，RNAiFold，一个逆折叠算法，确定所有序列的最小自由能结构是相同的结构域的利益。差异超过1个核苷酸的序列被聚类。然后，从RNAiFold输出的每个簇中随机选择一个序列进行BLAST，我们在输出命中中检索病毒和细胞序列。作为原理的证明，我们提出了对应于果蝇TAF6的编码区的数据，TAF6是一种转录因子相关蛋白，其编码区内含有可能折叠成IRES样亚结构域的结构基序。该RNA区域显示出偏好的密码子使用，如从RNA水平上的结构约束所预测的，其在环中具有保守的IRES结构基序，并且有趣的是，其具有赋予组织培养细胞中的翻译的内部起始的能力。
Internal ribosome entry site (IRES) elements govern protein synthesis of mRNAs that bypass cap-dependent translation inhibition under stress conditions. Picornavirus IRES are cis-acting elements, organized in modular domains that recruit the ribosome to internal mRNA sites. The aim of this study was to retrieve short RNA sequences with the capacity to adopt RNA folding patterns conserved with IRES structural subdomains, likely corresponding to RNA modules. We have applied a new program, RNAiFold, an inverse folding algorithm that determines all sequences whose minimum free energy structure is identical to that of the structural domains of interest. Sequences differing by more than 1 nt were clustered. Then, BLASTing one randomly chosen sequence from each cluster of the RNAiFold output, we retrieved viral and cellular sequences among output hits. As a proof of principle, we present the data corresponding to a coding region of Drosophila melanogaster TAF6, a transcription factor-associated protein that contains a structural motif within its coding region potentially folding into an IRES -like subdomain. This RNA region shows a biased codon usage, as predicted from structural constraints at the RNA level, it harbors conserved IRES structural motifs in loops, and interestingly, it has the capacity to confer internal initiation of translation in tissue culture cells.