proteins with mrna expression and stability including and tests for agents which affect their function.

摘要

mRNA degradation is an important control point in the regulation of gene expression and has been shown to be linked to the process of translation. One clear example of this linkage is the observation that nonsense mutations accelerate the degradation of mRNAs. In this report we demonstrate that a subset of the mof alleles (maintenance of frame) in yeast, which were isolated as chromosomal mutations that increased the frameshifting efficiency at the L-A virus frameshift site and caused loss of the L-A satellite virus M1, also affect the nonsense-mediated mRNA decay pathway. The levels of nonsense-containing mRNAs were elevated in cells harboring the mof4-1 alleles. Furthermore, mof4-1 is allelic to UPF1, which has been demonstrated to be involved in the nonsense-mediated mRNA decay pathway. Although cells harboring the mof4-1 allele lose the M1 virus, the other f alleles (i.e., upf1, upf2 and upf3) involved in nonsense-mediated mRNA decay maintain M1. The ifs1 and ifs2 alleles previously identified as mutations that enhance frameshifting at the -1 ribosomal frameshift signal from the mouse mannary tumor virus were shown to be allelic to the UPF2 and UPF1 genes, respectively, and both ifs strains maintained M1. The mof4-1 strain is more sensitive to the aminoglycoside paromomycin than a upf1Δ strain, and frameshifting efficiency increases in a mof4-1 strain grown in the presence of paromomycin. These results indicate that the upf1p has a dual function in both translation and mRNA turnover.