分析 CUGBP1 的靶标可以鉴定介导快速 mRNA 降解的 GU-重复序列。
Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay.
机构信息
Center for Infectious Diseases and Microbiology Translational Research, Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
出版信息
Mol Cell Biol. 2010 Aug;30(16):3970-80. doi: 10.1128/MCB.00624-10. Epub 2010 Jun 14.
Abstract
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.
摘要
CUG 重复结合蛋白 1（CUGBP1）通过与富含 GU 的元件（GRE）结合来介导选择性的 mRNA 降解，这些 GRE 包含在寿命短的转录物的 3'非翻译区（UTR）中发现的 UGUUUGUUUGU 序列。我们使用抗 CUGBP1 抗体从 HeLa 细胞质提取物中免疫沉淀 CUGBP1，并使用寡核苷酸微阵列分析相关的转录物。我们鉴定了 613 个 CUGBP1 的潜在 mRNA 靶标，并发现 UGUUUGUUUGU GRE 序列和 GU 重复序列在这些靶标的 3'UTR 中都高度富集。我们表明 CUGBP1 特异性结合 GU 重复序列，并且将该序列插入β珠蛋白报告转录本的 3'UTR 中会使转录本不稳定。基于这些结果，我们重新定义了 GRE，以包含该 GU 重复序列。我们的结果表明，CUGBP1 协调调节涉及细胞生长、细胞运动和细胞凋亡的转录物网络的 mRNA 降解。
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