Henderson B R, Kühn L C
MRC Laboratory of Molecular Biology, Cambridge, UK.
Prog Mol Subcell Biol. 1997;18:117-39. doi: 10.1007/978-3-642-60471-3_6.
In this chapter, we have focused on the biochemistry of IRP-1 and the features which distinguish it from the related RNA-binding protein, IRP-2. IRP-1 is the cytoplasmic isoform of the enzyme aconitase, and, depending on iron status, may switch between enzymatic and RNA-binding activities. IRP-1 and IRP-2 are trans-acting regulators of mRNAs involved in iron uptake, storage and utilisation. The finding of an IRE in the citric acid cycle enzymes, mitochondrial aconitase and succinate dehydrogenase, suggests that the IRPs may also influence cellular energy production. These two proteins appear to bind RNAs with different but overlapping specificity, suggesting that they may regulate the stability or translation of as yet undefined mRNA targets, possibly extending their regulatory function beyond that of iron homeostasis. The interaction between the IRPs and the IRE represents one of the best characterised model systems for posttranscriptional gene control, and given that each IRP can also recognise its own unique set of RNAs, the search for new in vivo mRNA targets is expected to provide yet more surprises and insights into the fate of cytoplasmic mRNAs.
在本章中，我们重点关注了铁调节蛋白1（IRP-1）的生物化学特性以及它与相关RNA结合蛋白铁调节蛋白2（IRP-2）的区别。IRP-1是顺乌头酸酶的胞质同工型，根据铁的状态，它可以在酶活性和RNA结合活性之间切换。IRP-1和IRP-2是参与铁摄取、储存和利用的mRNA的反式作用调节因子。在柠檬酸循环酶、线粒体顺乌头酸酶和琥珀酸脱氢酶中发现铁反应元件（IRE），表明IRP可能也会影响细胞能量产生。这两种蛋白质似乎以不同但重叠的特异性结合RNA，这表明它们可能调节尚未确定的mRNA靶标的稳定性或翻译，可能将其调节功能扩展到铁稳态之外。IRP与IRE之间的相互作用代表了转录后基因调控中最具特征的模型系统之一，而且鉴于每个IRP还能识别其自身独特的RNA集合，寻找新的体内mRNA靶标有望为细胞质mRNA的命运带来更多惊喜和见解。
