Wiesenberger G, Waldherr M, Schweyen R J
Institut für Mikrobiologie und Genetik, Universität Wien, Vienna, Austria.
J Biol Chem. 1992 Apr 5;267(10):6963-9.
RNA splicing defects in mitochondrial intron mutants can be suppressed by a high dosage of several proteins encoded by nuclear genes. In this study we report on the isolation, nucleotide sequence, and possible functions of the nuclear MRS2 gene. When present on high copy number plasmids, the MRS2 gene acts as a suppressor of various mitochondrial intron mutations, suggesting that the MRS2 protein functions as a splicing factor. This notion is supported by the observations that disruption of the single chromosomal copy of the MRS2 gene causes (i) a pet- phenotype and (ii) a block in mitochondrial RNA splicing of all four mitochondrial group II introns, some of which are efficiently self-splicing in vitro. In contrast, the five group I introns monitored here are excised from pre-mRNA in a MRS2-disrupted background although at reduced rates. So far the MRS2 gene product is unique in that it is essential for splicing of all four group II introns, but relatively unimportant for splicing of group I introns. In strains devoid of any mitochondrial introns the MRS2 gene disruption still causes a pet- phenotype and cytochrome deficiency, although the standard pattern of mitochondrial translation products is produced. Therefore, apart from RNA splicing, the absence of the MRS2 protein may disturb the assembly of mitochondrial membrane complexes.
线粒体内含子突变体中的RNA剪接缺陷可被几种核基因编码的蛋白质的高剂量所抑制。在本研究中，我们报告了核MRS2基因的分离、核苷酸序列及其可能的功能。当存在于高拷贝数质粒上时，MRS2基因可作为多种线粒体内含子突变的抑制因子，这表明MRS2蛋白作为一种剪接因子发挥作用。这一观点得到了以下观察结果的支持：MRS2基因单染色体拷贝的破坏会导致（i）pet-表型，以及（ii）所有四个线粒体II类内含子的线粒体RNA剪接受阻，其中一些内含子在体外可有效进行自我剪接。相比之下，尽管速率降低，但在此监测的五个I类内含子在MRS2破坏的背景下仍可从前体mRNA中切除。到目前为止，MRS2基因产物的独特之处在于，它对所有四个II类内含子的剪接至关重要，但对I类内含子的剪接相对不重要。在没有任何线粒体内含子的菌株中，尽管产生了标准模式的线粒体翻译产物，但MRS2基因的破坏仍然会导致pet-表型和细胞色素缺乏。因此，除了RNA剪接外，MRS2蛋白的缺失可能会干扰线粒体膜复合物的组装。
