Jaeger Sophie, Barends Sharief, Giegé Richard, Eriani Gilbert, Martin Franck
Département Mécanismes et Macromolécules de la Synthèse Protéique et Cristallogenèse, UPR 9002, Institut de Biologie Moléculaire et Cellulaire du CNRS, 15, rue René Descartes, 67084 Strasbourg cedex, France.
Biochimie. 2005 Sep-Oct;87(9-10):827-34. doi: 10.1016/j.biochi.2005.03.012. Epub 2005 Apr 12.
Histone proteins are essential components of eukaryotic chromosomes. In metazoans, they are produced from the so-called replication-dependent histone genes. The biogenesis of histones is tightly coupled to DNA replication in a stoichiometric manner because an excess of histones is highly toxic for the cell. Therefore, a strict cell cycle-regulation of critical factors required for histone expression ensures exclusive S-phase expression. This review focuses on the molecular mechanisms responsible for such a fine expression regulation. Among these, a large part will be dedicated to post-transcriptional events occurring on histone mRNA, like histone mRNA 3' end processing, nucleo-cytoplasmic mRNA export, translation and mRNA degradation. Many factors are involved, including an RNA-binding protein called HBP, also called SLBP (for hairpin- or stem-loop-binding protein) that binds to a conserved hairpin located in the 3' UTR part of histone mRNA. HBP plays a pivotal role in the expression of histone genes since it is necessary for most of the steps of histone mRNA metabolism in the cell. Moreover, the strict S-phase expression pattern of histones is achieved through a fine cell cycle-regulation of HBP. A large part of the discussion will be centered on the critical role of HBP in histone biogenesis.
组蛋白是真核生物染色体的重要组成部分。在多细胞动物中，它们由所谓的复制依赖型组蛋白基因产生。组蛋白的生物合成以化学计量的方式与DNA复制紧密偶联，因为过量的组蛋白对细胞具有高度毒性。因此，对组蛋白表达所需关键因子进行严格的细胞周期调控可确保仅在S期表达。本综述聚焦于负责这种精细表达调控的分子机制。其中，很大一部分将致力于组蛋白mRNA上发生的转录后事件，如组蛋白mRNA 3'末端加工、核质mRNA输出、翻译和mRNA降解。涉及许多因子，包括一种名为HBP（也称为SLBP，即发夹或茎环结合蛋白）的RNA结合蛋白，它与位于组蛋白mRNA 3'UTR部分的保守发夹结合。HBP在组蛋白基因的表达中起关键作用，因为它是细胞中组蛋白mRNA代谢大多数步骤所必需的。此外，组蛋白严格的S期表达模式是通过对HBP进行精细的细胞周期调控实现的。大部分讨论将围绕HBP在组蛋白生物合成中的关键作用展开。
