Rossignol Fabrice, Vaché Christel, Clottes Eric
Laboratoire Inter-Universitaire de Biologie des Activités Physiques et Sportives, Faculté de Médecine, 28 Place Henri Dunant, 63001 Clermont-Ferrand Cedex, France.
Gene. 2002 Oct 16;299(1-2):135-40. doi: 10.1016/s0378-1119(02)01049-1.
Hypoxia-inducible factor 1 is a heterodimeric transcription factor, made up of two subunits called HIF-1alpha and aryl receptor nuclear translocator, that regulates the expression of genes associated with adaptation to reduced oxygen pressure. The HIF-1alpha messenger RNA (mRNA) and protein are both up-regulated in common human cancers where this transcription factor is known to be involved in tumour progression. In renal carcinoma, a natural antisense of HIF-1alpha transcript (aHIF) that is complementary to the 3'untranslated region of HIF-1alpha mRNA has been described. Here, we provide a grown work for further characterisation of this natural antisense and we show that: (1) aHIF is widely expressed in normal foetal and adult human tissues as in tumour tissues. Foetal aHIF expression level is higher than adult one and high enough to affect the HIF-1alpha mRNA/aHIF transcripts ratio; (2) aHIF could expose AU rich elements present in the 3' untranslated region of HIF-1alpha mRNA and thus possibly increase the degradation speed of HIF-1alpha mRNA; and (3) aHIF promoter possesses several putative hypoxia response elements which could explain the overexpression of aHIF under hypoxic conditions, creating a negative loop of regulation of HIF-1alpha expression.
缺氧诱导因子1是一种异二聚体转录因子，由两个亚基组成，分别称为HIF-1α和芳香烃受体核转运蛋白，它可调节与适应低氧压力相关的基因表达。在已知该转录因子参与肿瘤进展的常见人类癌症中，HIF-1α信使核糖核酸（mRNA）和蛋白质均上调。在肾癌中，已描述了一种与HIF-1α mRNA的3'非翻译区互补的HIF-1α转录本的天然反义RNA（aHIF）。在此，我们提供了一项进一步表征这种天然反义RNA的深入研究，并表明：（1）aHIF在正常胎儿和成人组织以及肿瘤组织中广泛表达。胎儿aHIF表达水平高于成人，且高到足以影响HIF-1α mRNA/aHIF转录本的比例；（2）aHIF可暴露HIF-1α mRNA 3'非翻译区中存在的富含AU的元件，从而可能提高HIF-1α mRNA的降解速度；（3）aHIF启动子拥有几个假定的缺氧反应元件，这可以解释缺氧条件下aHIF的过表达，从而形成HIF-1α表达的负调控环。
