Shen W C, Stanford D R, Hopper A K
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
Genetics. 1996 Jun;143(2):699-712. doi: 10.1093/genetics/143.2.699.
To understand the role of Los1p in pre-tRNA splicing, we sought los1 multicopy suppressors. We found SOL1 that suppresses both point and null LOS1 mutations. Since, when fused to the Ga14p DNA-binding domain, Los1p activates transcription, we tested whether Los1p regulates SOL1. We found that las1 mutants have depleted levels of SOL1 mRNA and Sol1p. Thus, LOS1 appears to positively regulate SOL1. SOL1 belongs to a multigene family with at least two additional members, SOL2 and SOL3. Sol proteins have extensive similarity to an unusual group of glucose-6-phosphate dehydrogenases. As the similarities are restricted to areas separate from the catalytic domain, these G6PDs may have more than one function. The SOL family appears to be unessential since cells with a triple disruption of all three SOL genes are viable. SOL gene disruptions negatively affect tRNA-mediated nonsense suppression and the severity increases with the number of mutant SOL genes. However, tRNA levels do not vary with either multicopy SOL genes or with SOL disruptions. Therefore, the Sol proteins affect tRNA expression/ function at steps other than transcription or splicing. We propose that LOS1 regulates gene products involved in tRNA expression/function as well as pre-tRNA splicing.
为了了解Los1p在tRNA前体剪接中的作用,我们寻找了los1多拷贝抑制子。我们发现SOL1可以抑制LOS1的点突变和无效突变。由于当与Gal4p DNA结合结构域融合时,Los1p会激活转录,我们测试了Los1p是否调控SOL1。我们发现las1突变体中SOL1 mRNA和Sol1p的水平降低。因此,LOS1似乎正向调控SOL1。SOL1属于一个多基因家族,至少还有另外两个成员SOL2和SOL3。Sol蛋白与一组不同寻常的葡萄糖-6-磷酸脱氢酶有广泛的相似性。由于这些相似性仅限于与催化结构域分开的区域,这些葡萄糖-6-磷酸脱氢酶可能具有不止一种功能。SOL家族似乎并非必需,因为所有三个SOL基因都被三重破坏的细胞仍然存活。SOL基因的破坏会对tRNA介导的无义抑制产生负面影响,并且随着突变的SOL基因数量增加,这种影响的严重程度也会增加。然而,tRNA水平并不会随着多拷贝SOL基因或SOL基因的破坏而变化。因此,Sol蛋白在转录或剪接以外的步骤影响tRNA的表达/功能。我们提出,LOS1调控参与tRNA表达/功能以及tRNA前体剪接的基因产物。