Preferential expression of an intact WRN gene in Werner syndrome cell lines in which a normal chromosome 8 has been introduced

Werner syndrome (WS) is a premature aging syndrome caused by mutations in t he WRN gene. All mutations of the WRN gene reported thus far are predicted to produce the truncated WRN proteins. The mRNAs that contain chain-termina tion mutations are supposed to be unstable due to degradation by nonsense-m ediated mRNA decay (NMD). In the present study, we investigated the express ions of intact and nonsense-mutated WRN genes in Werner syndrome cell lines in which a normal chromosome 8 had been introduced by microcell fusion. We demonstrate here that the expression of the mutated WRN gene that produces nonsense mRNAs remains at low levels, resulting in the preferential expres sion of the intact WRN gene in the WS microcell hybrids. This result suppor ts the idea that imperfect messages containing premature termination codons are eliminated by the RNA surveillance system, suggesting the significance of the NMD mechanism in the etiology of Werner syndrome. (C) 2001 Academic Press.