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 the WRN gene. All mutations of the WRN gene reported thus far are predicted to produce the truncated WRN proteins. The mRNAs that contain chain-termination mutations are supposed to be unstable due to degradation by nonsense-mediated mRNA decay (NMD). In the present study, we investigated the expressions 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 expression of the intact WRN gene in the WS microcell hybrids. This result supports 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.
Kashino
G
G
Laboratory of Radiation and Life Science, Department of Health Sciences, School of Pharmaceutical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Kodama
S
S
Suzuki
K
K
Oshimura
M
M
Watanabe
M
M
D002460:Cell Line; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D018389:Codon, Nonsense; D004265:DNA Helicases / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005090:Exodeoxyribonucleases; D015870:Gene Expression; D006801:Humans; D006822:Hybrid Cells; D010641:Phenotype; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases; D014898:Werner Syndrome / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D000071657:Werner Syndrome Helicase
D018389:Codon, Nonsense; D018076:DNA, Complementary; D012333:RNA, Messenger; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase