Kato Junji, Niitsu Yoshiro
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Int J Hematol. 2002 Oct;76(3):208-12. doi: 10.1007/BF02982789.
Ferritin, composed of H-subunits and L-subunits, plays important roles in iron storage and in the control of intracellular iron distribution. Synthesis of both subunits is controlled by common cytoplasmic proteins, iron regulatory proteins (IRP-1 and IRP-2) that bind to the iron-responsive element (IRE) in the 5'-untranslated region of ferritin messenger RNA (mRNA). When intracellular iron is scarce, IRPs display IRE binding to suppress translation of mRNA. When cellular iron is abundant, IRPs become inactivated (IRP-1) or degraded (IRP-2). In the last few years, IRE mutations that cause disorders due to dysregulation of ferritin subunit synthesis have been identified. Hereditary hyperferritinemia-cataract syndrome is associated with point mutations or deletions in the IRE of L-subunit mRNA and is characterized by constitutively increased synthesis of L-subunits but is unrelated to iron overload. A single-point mutation in the IRE of H-subunit mRNA in members of a family affected with dominantly inherited iron overload has been reported. This review summarizes the current understanding of the translational disorders caused by IRE mutations in ferritin mRNA.
铁蛋白由H亚基和L亚基组成，在铁储存及细胞内铁分布的调控中发挥重要作用。这两个亚基的合成均受共同的胞质蛋白——铁调节蛋白（IRP-1和IRP-2）的控制，这些蛋白可与铁蛋白信使核糖核酸（mRNA）5'非翻译区的铁反应元件（IRE）结合。当细胞内铁缺乏时，IRP会与IRE结合以抑制mRNA的翻译。当细胞内铁充足时，IRP会失活（IRP-1）或降解（IRP-2）。在过去几年中，已发现因铁蛋白亚基合成失调而导致疾病的IRE突变。遗传性高铁蛋白血症-白内障综合征与L亚基mRNA的IRE中的点突变或缺失有关，其特征是L亚基的合成持续增加，但与铁过载无关。据报道，在一个受显性遗传铁过载影响的家族成员中，H亚基mRNA的IRE发生了单点突变。本综述总结了目前对铁蛋白mRNA中IRE突变引起的翻译障碍的认识。
