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- W2155345824 abstract "TIA-1 and TIAR are a pair of related RNA-binding proteins which have been implicated in apoptosis. We show that chicken DT40 cells with both tia-1 alleles and one tiarallele disrupted (tia-1(−/−)tiar(−/+) cells) are viable. However, their growth and survival in medium containing low serum levels is significantly reduced compared with DT40 cells. The remaining intact tiar allele intia-1(−/−)tiar(−/+) cells can only be disrupted if TIA-1 expression is first restored to the cells by transfection of a TIA-1 expression vector. We conclude that DT40 cells require either TIA-1 or TIAR for viability. TIA-1 overexpression intia-1(−/−)tiar(−/+) cells leads to a radical drop in TIAR levels, by inducing efficient splicing of twotiar alternative exons carrying in-frame stop codons. In wild-type DT40 cells, tiar transcripts including these exons can also be detected. These transcripts increase significantly in abundance in cycloheximide-treated cells, suggesting that splicing of the exons exposes mRNAs to nonsense-mediated mRNA decay. TIA-1 or TIAR depletion leads to a marked drop in splicing of the exons. The human tiar gene contains a corresponding pair of TIA-1-inducible alternative exons, and we show that there is very high sequence conservation between chickens and humans of the exon pair and parts of the flanking introns. The TIA-1/TIAR responsiveness of these alternative tiar exons is likely to be of physiological importance for controlling TIAR levels." @default.
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- W2155345824 date "2003-03-01" @default.
- W2155345824 modified "2023-09-30" @default.
- W2155345824 title "TIA-1 or TIAR Is Required for DT40 Cell Viability" @default.
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- W2155345824 doi "https://doi.org/10.1074/jbc.m212378200" @default.
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