Biochemistry and Genetics Otago, University of Otago, Dunedin, New Zealand.
RNA Biol. 2011 Sep-Oct;8(5):792-801. doi: 10.4161/rna.8.5.16037. Epub 2011 Sep 1.
Iron-responsive elements (IREs) function in the 5' or 3' untranslated regions (UTRs) of mRNAs as post-transcriptional structured cis-acting RNA regulatory elements. One known functional mechanism is the binding of Iron Regulatory Proteins (IRPs) to 5' UTR IREs, reducing translation rates at low iron levels. Another known mechanism is IRPs binding to 3' UTR IREs in other mRNAs, increasing RNA stability. Experimentally proven elements are quite small, have some diversity of sequence and structure, and functional genes have similar pseudogenes in the genome. This paper presents two new IRE covariance models, comprising a new IRE clan in the RFAM database to encompass this variation without over-generalisation. Two IRE models rather than a single model is consistent with experimentally proven structures and predictions. All of the IREs with experimental support are modelled. These two new models show a marked increase in the sensitivity and specificity in detection of known iron-responsive elements and ability to predict novel IREs.
铁反应元件 (IREs) 在 mRNA 的 5' 或 3' 非翻译区 (UTRs) 中作为转录后结构的顺式作用 RNA 调节元件发挥作用。一种已知的功能机制是铁调节蛋白 (IRP) 与 5' UTR IREs 结合，在低铁水平下降低翻译速率。另一种已知的机制是 IRP 结合到其他 mRNA 的 3' UTR IREs 上，增加 RNA 稳定性。经过实验验证的元件非常小，具有一定的序列和结构多样性，并且功能基因在基因组中具有相似的假基因。本文提出了两种新的 IRE 协变模型，包括 RFAM 数据库中的一个新的 IRE 族，以在不过度泛化的情况下包含这种变异性。两个 IRE 模型而不是单个模型与经过实验验证的结构和预测一致。所有具有实验支持的 IRE 都进行了建模。这两个新模型在检测已知的铁反应元件的灵敏度和特异性以及预测新的 IRE 方面有显著提高。
