Alternative 5 %26apos; Untranslated Regions Are Involved in Expression Regulation of Human Heme Oxygenase-1

作者：Kramer Marcel^*; Sponholz Christoph; Slaba Monique; Wissuwa Bianka; Claus Ralf A; Menzel Uwe; Huse Klaus; Platzer Matthias; Bauer Michael

来源：PLos One, 2013, 8(10): UNSP e77224.

DOI：10.1371/journal.pone.0077224

The single nucleotide polymorphism rs2071746 and a (GT)(n) microsatellite within the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or outcome in a variety of diseases. Most of these associations involve either release of heme or oxidative stress. Both polymorphisms are localized in the promoter region, but previously reported correlations with heme oxygenase-1 expression remain not coherent. This ambiguity suggests a more complex organization of the 5%26apos; gene region which we sought to investigate more fully. %26lt;br%26gt;We evaluated the 5` end of HMOX1 and found a novel first exon 1a placing the two previously reported polymorphisms in intronic or exonic positions within the 5%26apos; untranslated region respectively. Expression of exon 1a can be induced in HepG2 hepatoma cells by hemin and is a repressor of heme oxygenase-1 translation as shown by luciferase reporter assays. Moreover, minigene approaches revealed that the quantitative outcome of alternative splicing within the 5%26apos; untranslated region is affected by the (GT)(n) microsatellite. %26lt;br%26gt;This data supporting an extended HMOX1 gene model and provide further insights into expression regulation of heme oxygenase-1. Alternative splicing within the HMOX1 5%26apos; untranslated region contributes to translational regulation and is a mechanistic feature involved in the interplay between genetic variations, heme oxygenase-1 expression and disease outcome.

• 出版日期2013-10-2