We used computational algorithms to find conserved sequences in the 3' untranslated region (UTR) of transcripts that exhibited rapid decay in primary human T cells and found that the consensus sequence UGUUUGUUUGU, which we have termed a GU-rich element (GRE), was enriched in short-lived transcripts. Using a tet-off reporter system, we showed that insertion of GRE-containing sequences from c-jun, jun B, or TNF receptor 1B, but not mutated GRE sequences, into the 3'UTR of a beta-globin transcript conferred instability on the otherwise stable beta-globin transcript. CUG-binding protein 1 (CUGBP1) was identified as the major GRE-binding activity in cytoplasmic extracts from primary human T cells based on supershift and immunoprecipitation assays. siRNA-mediated knockdown of CUGBP1 in HeLa cells caused stabilization of GRE-containing transcripts, suggesting that CUGBP1 is a mediator of GRE-dependent mRNA decay. Overall, our results suggest that the GRE mediates coordinated mRNA decay by binding to CUGBP1.
We investigated the correlation between age and total RNA levels in long-lived and control lines of Drosophila melanogaster. Total RNA was extracted at 10 ages from 1-63 days posteclosion from 3 inbred lines, with replication. Three different methods of RNA quantitation gave highly correlated estimates. Total RNA declined substantially with age, exhibiting a dramatic drop in the first few days of adult life. We find no evidence for a causal relationship between adult longevity and total RNA levels, since long-lived and control lines exhibited similar patterns of age-related RNA decline. These observations suggest that the dramatic decline in total RNA that occurs early in adult life does not explain the twofold differences in life span between lines. The pattern of age-specific decline coincides with published observations on age-specific metabolic rates, and suggests that 14-day-old flies are functionally senescent.
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