Previously we characterized [NSI+] determinant, that possesses the features of a yeast prion. This determinant causes the nonsense suppression in strains that bear different N-substituted variants of Sup35p, which is a translation release factor eRF3. As a result of the genomic screen, we identified VTS1, the overexpression of which is a phenotypic copy of [NSI+]. Here, we analyzed the influence of SUP35 and VTS1 on [NSI+]. We demonstrated nonsense suppression in the [NSI+] strains, which appears when SUP35 expression was decreased or against a background of general defects in the fidelity of translation termination. [NSI+] has also been shown to increase VTS1 mRNA amounts. These findings facilitate the insight into the mechanisms of nonsense suppression in the [NSI+] strains and narrow the range of candidates for [NSI+] determinant.