Nucleolar dominance and rRNA gene dosage control: a paradigm for transcriptional regulation via an epigenetic on/off switch
Nucleolar dominance and rRNA gene dosage control: a paradigm for transcriptional regulation via an epigenetic on/off switch
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DOI：
10.1002/9780470988626.ch7
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发表时间：
2005-01-01
期刊：
影响因子：
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通讯作者：
Pikaard, Craig S.
中科院分区：
文献类型：
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作者：
Neves, Nuno;Viegas, Wanda;Pikaard, Craig S.
在真核生物中，构建核糖体需要四个核糖体RNA(RRNAs)和85美元的蛋白质，核糖体是负责所有蛋白质合成的分子机器。因此，核糖体生物发生的调控对于调控细胞生长至关重要，并且与调控增殖的机制密切相关(Moss&Stefan ovsky，2002；Warner，1999)。构建真核核糖体是一项复杂的工作，需要所有三个核DNA依赖的RNA聚合酶转录系统的协调，即RNA聚合酶I、II和III。RNA聚合酶I负责转录一个基本上相同的基因大家族，每个基因编码一个45S(S？斯维德伯格单位；描述超速离心时的沉降行为)的初级转录本，然后被加工成组成核糖体催化核心的四个rRNA中的三个，即18S、5.8 S和25/28S(植物和酵母中的25S；哺乳动物中的28S；Pederson&Politz，2000)(Grummt，1999)。按照惯例，由RNA聚合酶I转录的基因被称为rRNA基因，或统称为rDNA。RNA聚合酶II负责核糖体蛋白基因的转录。RNA聚合酶III转录编码核糖体第四结构RNA的重复基因，其大小为5S；因此，这些基因按照惯例被称为5S基因。本章重点介绍由RNA聚合酶I转录的rRNA基因(RDNA)的调控。在真核细胞中，rRNA基因以数百到数千个拷贝的形式存在，在跨越数百万个碱基对的一个或多个染色体上以头尾相连的重复形式组织(图7.1A)。由RNA聚合酶I转录的rRNA基因产生核仁，核仁是细胞核中最明显的部分，也是细胞组装核糖体的工厂(Hernandez-Verdun等人，2002；Leung&Lamond，2003；Schwarzacher&Mosgoeller，2000；Shaw&Jordan，1995)(图7.1 B)。因此，rRNA基因定位的位置被称为核仁组织区域，或NORs(McClintock，1934)。最近的几篇综述讨论了rRNA基因的组织和转录特征及其在细胞代谢中的核心作用(Grummt，2003；Moss&Stefan ovsky，2002；Neves等人，2005；
In eukaryotes, four ribosomal RNAs (rRNAs) and $85 proteins are needed to build ribosomes, the molecular machines responsible for all protein synthesis. The regulation of ribosome biogenesis is therefore crucial for regulating cell growth and is closely tied to the mechanisms that regulate proliferation (Moss & Stefanovsky, 2002; Warner, 1999). Building a eukaryotic ribosome is a complicated enterprise, requiring the coordination of all three nuclear DNA-dependent RNA polymerase transcription systems, namely RNA polymerases I, II and III. RNA polymerase I is responsible for transcribing a large family of essentially identical genes, each of which encodes a 45S (S ¼ Svedberg unit; describes sedimentation behavior upon ultracentrifugation) primary transcript that is subsequently processed into three of the four rRNAs that form the catalytic core of the ribosome, namely rRNAs of 18S, 5.8 S and 25/28S (25S in plants and yeast; 28S in mammals; Pederson & Politz, 2000)(Grummt, 1999). By convention, the genes transcribed by RNA polymerase I are known as rRNA genes or, collectively, as rDNA. RNA polymerase II is responsible for the transcription of the ribosomal protein genes. RNA polymerase III transcribes the repetitive genes encoding the fourth structural RNA of the ribosomes, which is 5S in size; thus these genes are known by convention as 5S genes. This chapter focuses on the regulation of the rRNA genes (rDNA) transcribed by RNA polymerase I. rRNA genes are present in hundreds to thousands of copies in eukaryotic cells, organized as head-to-tail repeats at one or more chromosomal loci that span millions of base pairs (Figure 7.1 A). Transcription of the rRNA genes by RNA polymerase I gives rise to the nucleolus, the most conspicuous compartment of the nucleus and the cell’s factory for ribosome assembly (Hernandez-Verdun et al., 2002; Leung & Lamond, 2003; Schwarzacher & Mosgoeller, 2000; Shaw & Jordan, 1995)(Figure 7.1 B). As a result, the loci where rRNA genes are localized are termed nucleolar organizing regions, or NORs (McClintock, 1934). Several recent reviews have discussed the organization and transcriptional features of rRNA genes and their central role in cellular metabolism (Grummt, 2003; Moss & Stefanovsky, 2002; Neves et al., 2005;