PMID: 8608447Mar 1, 1996Paper

Evidence that the decay of nucleus-associated nonsense mRNA for human triosephosphate isomerase involves nonsense codon recognition after splicing

RNA
J Zhang, L E Maquat

Abstract

For most of the mammalian mRNAs that have been shown to be reduced in abundance by a nonsense or a frameshift mutation that generates a nonsense codon, reduction takes place while the mRNA is nucleus-associated rather than after the mRNA has been exported to the cytoplasm (reviewed in Maquat LE, 1995, RNA 1:453-465). A variety of mechanisms have been put forth to explain how a nonsense codon could affect the abundance of nuclear mRNA. Some mechanisms have implicated nonsense codon recognition in the nucleus prior to splicing. Among the best-studied nonsense transcripts that manifest nonsense-mediated alterations in nucleus-associated metabolism are those that derive from human alleles for the glycolytic enzyme triosephosphate isomerase (TPI). Nonsense codons within TPI transcripts have been shown to reduce the half-life of completely spliced TPI (mRNA that co-purifies with nuclei (Belgrader P et al., 1994, Mol Cell Biol 14:8219-8228). However, whether or not nonsense codon recognition within TPI transcripts takes place prior to or after splicing remained unresolved. To address this issue, codons that span two exons, i.e., are disrupted by an intron prior to pre-mRNA splicing, were converted to nonsense. If nonsense codon recogn...Continue Reading

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