NRF-1 - A TRANSACTIVATOR OF NUCLEAR-ENCODED RESPIRATORY GENES IN ANIMAL-CELLS
NRF-1 - A TRANSACTIVATOR OF NUCLEAR-ENCODED RESPIRATORY GENES IN ANIMAL-CELLS
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DOI：
10.1101/gad.4.6.1023
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发表时间：
1990-06-01
影响因子：
10.5
通讯作者：
SCARPULLA, RC
中科院分区：
文献类型：
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作者：
EVANS, MJ;SCARPULLA, RC
呼吸器的组装需要来自核和线粒体遗传系统的大量基因的协调表达。在脊椎动物中，整合这些不同基因组区段的活动以响应组织对呼吸能量的需求的分子机制尚不清楚。核呼吸因子1(NRF-1)的发现是解决这一问题的一个潜在途径，它是一种新的转录激活剂，由体细胞色素c启动子的突变和DNA结合分析定义。现在，在其他几个最近分离的核基因中观察到了功能性的NRF-1位点，这些基因的产物在线粒体中发挥功能。其中包括编码细胞色素c氧化酶(Vic亚单位)和还原酶(泛醌结合蛋白)复合体亚单位的基因。此外，在MRP RNA基因中还存在一个功能性的NRF-1位点，编码与线粒体DNA复制有关的核糖核蛋白内切酶的RNA基团。这些位点的合成寡聚体竞争性地取代与细胞色素c启动子结合的NRF-1。每个位点的NRF-1结合活性也具有相同的热能力，相互层析，并在每个识别序列中进行类似的鸟苷核苷酸接触。此外，NRF-1的体外识别与每个位点模拟截短细胞色素c启动子在体内表达的能力相关。在编码哺乳动物电子传输链结构成分的核基因以及线粒体DNA复制机制中，NRF-1结合位点的存在表明了一种通过核基因的协同调节来协调核和线粒体遗传系统的机制。
The assembly of the respiratory apparatus requires the coordinate expression of a large number of genes from both nuclear and mitochondrial genetic systems. In vertebrate organisms, the molecular mechanisms integrating the activities of these distinct genomic compartments in response to tissue demands for respiratory energy remain unknown. A potential inroad to this problem came with the discovery of nuclear respiratory factor 1 (NRF-1), a novel transcriptional activator defined by mutational and DNA binding analysis of the somatic cytochrome c promoter. Functional NRF-1 sites are now observed in several other recently isolated nuclear genes whose products function in the mitochondria. Among these are genes encoding subunits of the cytochrome c oxidase (subunit VIc) and reductase (ubiquinone-binding protein) complexes. In addition, a functional NRF-1 site resides in the MRP RNA gene encoding the RNA moeity of a ribonucleoprotein endonuclease involved in mitochondrial DNA replication. Synthetic oligomers of these sites competitively displace NRF-1 binding to the cytochrome c promoter. NRF-1-binding activities for each site also have the same thermal ability, copurify chromatographically, and make similar guanosine nucleotide contacts within each recogition sequence. Moreover, NRF-1 recognition in vitro correlates with the ability of each site to simulate expression in vivo from a truncated cytochrome c promoter. The presence of NRF-1-binding sites in nuclear genes encoding structural components of the mammalian electron transport chain, as well as the mitochondrial DNA replication machinery, suggests a mechanism for coordination of nuclear and mitochondrial genetic systems through the concerted modulation of nuclear genes.