Two covariance models for iron-responsive elements

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.