Cui Y, Dinman J D, Peltz S W
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Cancer Institute of New Jersey, Piscataway 08854, USA.
EMBO J. 1996 Oct 15;15(20):5726-36. doi: 10.1002/j.1460-2075.1996.tb00956.x.
The mof4-1 (maintenance of frame) allele in the yeast Saccharomyces cerevisiae was isolated as a chromosomal mutation that increased the efficiency of -1 ribosomal frameshifting at the L-A virus frameshift site and caused loss of M1, the satellite virus of L-A. Here, we demonstrate that strains harboring the mof4-1 allele inactivated the nonsense-mediated mRNA decay pathway. The MOF4 gene was shown to be allelic to UPF1, a gene whose product is involved in the nonsense-mediated mRNA decay pathway. Although cells harboring the mof4-1 allele of the UPF1 gene lose the M1 virus, mutations in other UPF genes involved in nonsense-mediated mRNA decay maintain the M1 virus. The mof4-1 strain is more sensitive to the aminoglycoside antibiotic paromomycin than a upf1 delta strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of this drug. Further, the ifs1 and ifs2 alleles previously identified as mutations that enhance frameshifting were shown to be allelic to the UPF2 and UPF1 genes, respectively, and both ifs strains maintained M1. These results indicate that mof4-1 is a unique allele of the UPF1 gene and that the gene product of the mof4-1 allele affects both -1 ribosomal frameshifting and mRNA turnover.
酵母酿酒酵母中的mof4-1(读框维持)等位基因是作为一种染色体突变被分离出来的,该突变提高了L-A病毒移码位点处-1核糖体移码的效率,并导致L-A的卫星病毒M1丢失。在此,我们证明携带mof4-1等位基因的菌株使无义介导的mRNA降解途径失活。MOF4基因被证明与UPF1等位,UPF1基因的产物参与无义介导的mRNA降解途径。虽然携带UPF1基因的mof4-1等位基因的细胞会丢失M1病毒,但参与无义介导的mRNA降解的其他UPF基因中的突变会使M1病毒得以保留。mof4-1菌株比upf1Δ菌株对氨基糖苷类抗生素巴龙霉素更敏感,并且在存在这种药物的情况下生长的mof4-1菌株中移码效率会增加。此外,先前被鉴定为增强移码的突变的ifs1和ifs2等位基因分别被证明与UPF2和UPF1基因等位,并且两个ifs菌株都保留了M1。这些结果表明mof4-1是UPF1基因的一个独特等位基因,并且mof4-1等位基因的基因产物影响-1核糖体移码和mRNA周转。