The mof4-1 (maintenance of frame) allele in the yeast Saccharomyces cerevisiae tvas isolated as a chromosomal mutation that increased the efficiency of -1 ribosomal frameshifting at the L-A virus frameshift site and caused loss of M(1), 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 M(1) virus, mutations in other UPF genes involved in nonsense-mediated mRNA decay maintain the M(1) 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 UPFI gene and that the gene product of the mof4-1 allele affects both -1 ribosomal frameshifting and mRNA turnover.