Normal transcription of the beta-hexosaminidase alpha-chain gene in the Ashkenazi Tay-Sachs mutation.
Tay-Sachs disease is a biochemically heterogeneous lysosomal storage disorder caused by lack of the A isoenzyme of beta-hexosaminidase; the underlying defect is a mutation in the gene encoding the alpha-chain. It has been shown that fibroblasts isolated from Tay-Sachs patients of Ashkenazi Jewish origin contain no alpha-chain mRNA detectable on Northern blots. We now have compared run-on transcription in nuclei isolated from three strains of Ashkenazi Tay-Sachs fibroblasts and from a strain of normal (IMR90) cells. Using alpha-chain and beta-chain cDNAs as probes, we found no difference in the relative amount of [32P]ribonucleotide added to nascent transcripts; the average ratio of alpha/beta hybridizable radioactivity was 1.3 and 1.4 for mutant and normal cells, respectively. The identity of the Tay-Sachs alpha-chain transcript was confirmed by competition hybridization with excess alpha-chain mRNA. The results indicate that the Ashkenazi Tay-Sachs mutation permits a normal level of transcription of the alpha-chain gene and points to a posttranscriptional defect, such as RNA processing, transport, or stability.
D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D011061:Poly A / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger; D013661:Tay-Sachs Disease / Q000201:enzymology / Q000235:genetics*; D014158:Transcription, Genetic; D001619:beta-N-Acetylhexosaminidases / Q000235:genetics*
D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D001619:beta-N-Acetylhexosaminidases