Analysis of CUGBP1 Targets Identifies GU-Repeat Sequences That Mediate Rapid mRNA Decay
Analysis of CUGBP1 Targets Identifies GU-Repeat Sequences That Mediate Rapid mRNA Decay
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DOI：
10.1128/mcb.00624-10
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发表时间：
2010-08-01
影响因子：
5.3
通讯作者：
Bohjanen, Paul R.
中科院分区：
文献类型：
--
作者：
Rattenbacher, Bernd;Beisang, Daniel;Bohjanen, Paul R.
CUG重复序列结合蛋白1（CUGBP 1）通过与短寿命转录物的3'非翻译区（UTR）中发现的含有序列UGUUUGUUGU的富含GU的元件（GRE）结合来介导选择性mRNA衰变。我们使用了抗CUGBP 1抗体免疫沉淀从HeLa细胞质提取物CUGBP 1和相关的成绩单使用寡核苷酸微阵列分析。我们鉴定了613个CUGBP 1的推定mRNA靶，并发现UGUUGUUUGU GRE序列和一个GU重复序列都高度富集在这些靶的3'UTR中。我们发现CUGBP 1特异性地结合到GU重复序列，并且将该序列插入到β-珠蛋白报告转录物的3' UTR中赋予转录物不稳定性。基于这些结果，我们重新定义了GRE，包括这个GU重复序列。我们的研究结果表明，CUGBP 1协调调节mRNA衰变的转录网络参与细胞生长，细胞运动和凋亡。
CUG-repeat binding protein 1 (CUGBP1) mediates selective mRNA decay by binding to GU-rich elements (GREs) containing the sequence UGUUUGUUUGU found in the 3' untranslated region (UTR) of short-lived transcripts. We used an anti-CUGBP1 antibody to immunoprecipitate CUGBP1 from HeLa cytoplasmic extracts and analyzed the associated transcripts using oligonucleotide microarrays. We identified 613 putative mRNA targets of CUGBP1 and found that the UGUUUGUUUGU GRE sequence and a GU-repeat sequence were both highly enriched in the 3' UTRs of these targets. We showed that CUGBP1 bound specifically to the GU-repeat sequence and that insertion of this sequence into the 3' UTR of a beta-globin reporter transcript conferred instability to the transcript. Based on these results, we redefined the GRE to include this GU-repeat sequence. Our results suggest that CUGBP1 coordinately regulates the mRNA decay of a network of transcripts involved in cell growth, cell motility, and apoptosis.