Frank D J, Roth M B
Division of Basic Sciences and Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
J Cell Biol. 1998 Mar 23;140(6):1321-9. doi: 10.1083/jcb.140.6.1321.
Regulation of ribosome synthesis is an essential aspect of growth control. Thus far, little is known about the factors that control and coordinate these processes. We show here that the Caenorhabditis elegans gene ncl-1 encodes a zinc finger protein and may be a repressor of RNA polymerase I and III transcription and an inhibitor of cell growth. Loss of function mutations in ncl-1, previously shown to result in enlarged nucleoli, result in increased rates of rRNA and 5S RNA transcription and enlarged cells. Furthermore, ncl-1 adult worms are larger, have more protein, and have twice as much rRNA as wild-type worms. Localization studies show that the level of NCL-1 protein is independently regulated in different cells of the embryo. In wild-type embryos, cells with the largest nucleoli have the lowest level of NCL-1 protein. Based on these results we propose that ncl-1 is a repressor of ribosome synthesis and cell growth.
核糖体合成的调控是生长控制的一个重要方面。到目前为止,对于控制和协调这些过程的因素知之甚少。我们在此表明,秀丽隐杆线虫基因ncl-1编码一种锌指蛋白,可能是RNA聚合酶I和III转录的抑制因子以及细胞生长的抑制剂。ncl-1功能缺失突变(先前已证明会导致核仁增大)会导致rRNA和5S RNA转录速率增加以及细胞增大。此外,ncl-1成年线虫体型更大,蛋白质含量更高,rRNA含量是野生型线虫的两倍。定位研究表明,NCL-1蛋白水平在胚胎的不同细胞中受到独立调控。在野生型胚胎中,核仁最大的细胞中NCL-1蛋白水平最低。基于这些结果,我们提出ncl-1是核糖体合成和细胞生长的抑制因子。