Ribosomes and Ribosomal Proteins: More Than Just ‘Housekeeping’-猫眼课题宝

DOI：

10.1002/9780470015902.a0005055.pub2

发表时间：

2012-07

期刊：

影响因子：

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中科院分区：

其他

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作者：

Anirban Chakraborty;N. Kenmochi

作为蛋白质合成的催化剂，无处不在的核糖体对所有生物都是必不可少的。在哺乳动物细胞中，核糖体由四种核糖体核糖核酸(RNA)和79种不同的核糖体蛋白组成。数百个编码核糖体RNA的基因在人类基因组中形成簇；相比之下，编码核糖体蛋白的基因广泛分布，尽管它们在功能上相关并协调表达。核糖体生物发生是一个严格控制的多步骤过程，需要大量的细胞能量。在过去的十年里，我们对核糖体的看法发生了显著的变化。在过去，核糖体被认为是细胞生存的关键。然而，现在已经清楚的是，核糖体生物发生中的缺陷会引起多效性效应，这可能会在人类的特定疾病条件下表现出来。核糖体蛋白以前被认为只起到看家的作用，现在已知具有许多核糖体外功能，包括监测核糖体的完整性。核心概念：所有三种RNA聚合酶、几种辅助蛋白和许多小核仁RNA以协调的方式发挥作用，以确保核糖体RNA(RRNAs)和核糖体蛋白(RPS)被正确合成并组装成具有功能活性的核糖体。真核生物、古生物和细菌的rRNAs和RPs的数量不同；然而，核糖体成分的功能在整个进化过程中在很大程度上是保守的。核仁是聚集在rDNA簇周围的核的一个亚室，是核糖体生产的主要场所。一般来说，RPS是碱性蛋白质，对核酸表现出特定的亲和力；然而，四种RPS具有酸性等电点。在人类中，编码rRNA的基因通常在基因组内以多个副本聚集在一起；而通常由单基因编码的RPS基因分散在基因组中。在过去的二十年里，RPS参与了许多不同于其在核糖体生物发生中的主要功能的细胞活动。P53肿瘤抑制蛋白是细胞对各种应激源反应的重要组成部分，通过涉及几个RP的监测机制来监测核糖体生物发生的保真度。核糖体生物发生的中断会引起“核仁压力”，从而触发P53信号通路，导致细胞周期停滞和细胞凋亡。RP基因的单倍性不足或编码核糖体生物发生所必需的蛋白质的基因突变可导致人类一类特定的疾病，称为核糖体病变，通常表现为显著的组织特异性缺陷和相关的多效性异常。关键词：核糖体；核糖体生物发生；核仁；核糖体RNA；核糖体蛋白；核糖体应激；p53；核糖体病

As the catalyst for protein synthesis, the omnipresent ribosome is essential to all organisms. In mammalian cells, the ribosome is composed of four ribosomal ribonucleic acid (RNA) species and 79 different ribosomal proteins. Several hundred copies of the genes encoding the ribosomal RNAs form clusters within the human genome; by contrast, the genes encoding the ribosomal proteins are widely dispersed, although they are functionally related and coordinately expressed. Ribosome biogenesis is a tightly controlled multi-step process that requires massive cellular energy. Over the past decade, our perception of the ribosome has changed significantly. In the past, ribosomes were considered critical for cellular survival. However, it has now become clear that defects in ribosome biogenesis cause pleiotropic effects that may manifest as specific disease conditions in humans. Ribosomal proteins, which were previously considered to play only a housekeeping role, are now known to have many extraribosomal functions, including the surveillance of ribosomal integrity. Key Concepts: All of the three RNA polymerases, several accessory proteins, and numerous small nucleolar RNAs act in a coordinated manner to ensure that ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) are properly synthesised and assembled into a functionally active ribosome. The numbers of rRNAs and RPs vary between eukaryotes, archaea, and bacteria; however, the functions of ribosomal components have been conserved to a substantial degree throughout evolution. The nucleolus, a sub-compartment of the nucleus that assembles around the rDNA clusters, is the major site of ribosome production. In general, RPs are basic proteins and exhibit specific affinities for nucleic acids; however, four RPs have acidic pI values. In humans, the genes encoding rRNAs are usually clustered together in multiple copies within the genome; whereas, the genes for the RPs, which are typically encoded by single genes, are scattered through out the genome. Over the past two decades, RPs have been implicated in many cellular activities that are distinct from their primary functions in ribosome biogenesis. The p53 tumour suppressor protein, an important component in the cellular response to a variety of stressors, monitors the fidelity of ribosome biogenesis through a surveillance mechanism that involves several RPs. The disruption of ribosome biogenesis causes ‘nucleolar stress’ that triggers the p53-signalling pathway, resulting in cell cycle arrest and apoptosis. Haploinsufficiency in RP genes or mutations in genes that encode proteins essential for ribosome biogenesis can lead to a specific class of diseases in humans, called ribosomopathies, which often manifest as prominent tissue-specific defects with associated pleiotropic anomalies. Keywords: ribosome; ribosome biogenesis; nucleolus; ribosomal RNAs; ribosomal proteins; ribosomal stress; P53; ribosomopathies

Ribosomes and Ribosomal Proteins: More Than Just ‘Housekeeping’

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