Stewart Stevens and Chris Brown, University of Otago
Paul Gardner, Wellcome Trust Sanger Institute, current address : University of Canterbury.
Click here for link to full text at RNA Biology.
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.
|3' UTR||HMGB1||Transcription factor that also acts as a cytokine in immune response.||Link|
|HAS3||Transmembrane protein that synthesises hyaluronan - a polysaccharide involved in connective tissue and in cell behaviour during embryonic development and inflammation.||Link|
|MGAT4A||Glycosyltransferase with several isoforms and potential physiological roles.||Link|
|VHL||Protein targeting the hypoxia-inducible transcription factor for polyubiquitination and degradation.||Link|
|LHFPL4||Product that appears to be a tetraspan transmembrane protein. It is not well studied but does have homology with TMHS which is reported to have a role in the morphogenesis of cilia in the ear.||Link|
|PLEKHA8||Adaptor protein that transfers glucosylceramide to specific sites for the synthesis of glycosphingolipids.||Link|
|FKTN||Transmembrane protein localised to the Golgi complex with a role in glycosylation.||Link|
|CDS||TMEM202||Transmembrane protein (inferred from protein domains via Uniprot) but has no known function.|
|Tom1L1||Adaptor protein thought to be involved in mitogenic signalling.||Link|
|DSTN||Protein with a functional role in actin depolymerisation and filament dynamics.||Link|
|ENPEP||Protease acting in the metabolism of angiotensin.||Link|
|SEC63||Protein forming part of a transmembrane complex. This complex transports other proteins across the membrane of the endoplasmic recticulum.||Link|
Click here to view the search results for the new IRE families with bit score cutoff 17 on the human genome at UCSC or here to directly access the interval file.
Click here to view the search results for the new IRE family 1 with bit score cutoff 19 on the human genome at UCSC or here to directly access the interval file.
Click here to view the search results for the new IRE family 2 with bit score cutoff 28 on the human genome at UCSC or here to directly access the interval file.
Click here to see the search results from all homologues obtained from Ensembl corresponding to genes with predicted IREs in humans.
Click here to see the search results from all homologues obtained from Homologene,NCBI corresponding to genes with predicted IREs in humans.
Page last update 3/3/2012 by CMB
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