期刊
MOLECULAR CELL
卷 29, 期 2, 页码 263-270出版社
CELL PRESS
DOI: 10.1016/j.molcel.2007.11.024
关键词
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资金
- NHLBI NIH HHS [R01 HL073719, R01 HL089249, R01 HL076779, R01 HL076779-04, HL 073719, R01 HL073719-04, HL 076779] Funding Source: Medline
- NIAID NIH HHS [R01 AI049494, R01 AI049494-05, K02 AI052170-02, K02 AI052170-03, R01 AI049494-04, K02 AI052170, R56 AI057484, R01 AI049494-03, K02 AI052170-01, R01 AI072068-01A1, R56 AI057484-01A3, AI 52170, R01 AI072068, AI 49494, K02 AI052170-05, K02 AI052170-04] Funding Source: Medline
- NICHD NIH HHS [T32 HD007381-13, T32 HD007381, T32 HD 007381, T32 HD007381-14] Funding Source: Medline
- NIDCR NIH HHS [T32 DE007288, T32 DE007288-11, T32 DE007288-12] Funding Source: Medline
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 1 B, 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.
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