Li L, Linning R M, Kondo K, Honda B M
Institute of Molecular Biology and Biochemistry and Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Mol Cell Biol. 1998 Feb;18(2):703-9. doi: 10.1128/MCB.18.2.703.
Eight different amber suppressor tRNA (suptRNA) mutations in the nematode Caenorhabditis elegans have been isolated; all are derived from members of the tRNA(Trp) gene family (K. Kondo, B. Makovec, R. H. Waterston, and J. Hodgkin, J. Mol. Biol. 215:7-19, 1990). Genetic assays of suppressor activity suggested that individual tRNA genes were differentially expressed, probably in a tissue- or developmental stage-specific manner. We have now examined the expression of representative members of this gene family both in vitro, using transcription in embryonic cell extracts, and in vivo, by assaying suppression of an amber-mutated lacZ reporter gene in animals carrying different suptRNA mutations. Individual wild-type tRNA(Trp) genes and their amber-suppressing counterparts appear to be transcribed and processed identically in vitro, suggesting that the behavior of suptRNAs should reflect wild-type tRNA expression. The levels of transcription of different suptRNA genes closely parallel the extent of genetic suppression in vivo. The results suggest that differential expression of tRNA genes is most likely at the transcriptional rather than the posttranscriptional level and that 5' flanking sequences play a role in vitro, and probably in vivo as well. Using suppression of a lacZ(Am) reporter gene as a more direct assay of suptRNA activity in individual cell types, we have again observed differential expression which correlates with genetic and in vitro transcription results. This provides a model system to more extensively study the basis for differential expression of this tRNA gene family.
在线虫秀丽隐杆线虫中已分离出8种不同的琥珀抑制tRNA(suptRNA)突变;所有这些突变均源自tRNA(Trp)基因家族的成员(近藤健、马科韦茨、R. H. 沃特斯顿和J. 霍奇金,《分子生物学杂志》215:7 - 19,1990年)。对抑制活性的遗传学分析表明,各个tRNA基因的表达存在差异,可能是以组织或发育阶段特异性的方式。我们现在已经在体外使用胚胎细胞提取物中的转录来研究这个基因家族代表性成员的表达,并在体内通过检测携带不同suptRNA突变的动物中琥珀突变的lacZ报告基因的抑制情况来进行研究。各个野生型tRNA(Trp)基因及其琥珀抑制对应物在体外的转录和加工方式似乎相同,这表明suptRNAs的行为应反映野生型tRNA的表达。不同suptRNA基因的转录水平与体内遗传抑制的程度密切平行。结果表明,tRNA基因的差异表达最有可能发生在转录水平而非转录后水平,并且5'侧翼序列在体外发挥作用,在体内可能也发挥作用。使用lacZ(Am)报告基因的抑制作为对单个细胞类型中suptRNA活性的更直接检测方法,我们再次观察到了与遗传和体外转录结果相关的差异表达。这提供了一个模型系统,可用于更广泛地研究这个tRNA基因家族差异表达的基础。