An RNA-protein complex links enhanced nuclear 3′ processing with cytoplasmic mRNA stabilization
An RNA-protein complex links enhanced nuclear 3′ processing with cytoplasmic mRNA stabilization
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DOI：
10.1038/emboj.2011.171
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发表时间：
2011-07-06
期刊：
影响因子：
11.4
通讯作者：
Liebhaber, Stephen A.
中科院分区：
文献类型：
--
作者：
Ji, Xinjun;Kong, Jian;Liebhaber, Stephen A.
转录后调控对基因调控至关重要。这些控制通常基于反式作用蛋白与靶RNA上的顺式作用基序的序列特异性结合。先前的研究已经揭示了KH结构域蛋白α CP与α珠蛋白mRNA的3' UTR C富集基序结合并有助于其细胞质稳定性。在这里，我们报告说，这个3'非翻译区α CP复合物调节成熟α珠蛋白mRNA的生产，通过增强3'加工的h α珠蛋白转录。我们继续证明，这种核活性反映了裂解和聚腺苷酸化反应的增强，并且α CP在体内与3'加工复合物的核心组分相互作用。与其核加工活性一致，我们的研究揭示α CP在h α-珠蛋白染色质位点共转录组装，并且这种装载选择性地富集在基因的3'末端。通过共同的RNA-蛋白质复合物证实的细胞核加工与细胞质稳定化的联系建立了整合对靶mRNA的稳健和持续表达至关重要的顺序控制的基础。The EMBO Journal（2011）30，2622-2633. doi：10.1038/daj.2011.171; 2011年5月27日在线发布
Post-transcriptional controls are critical to gene regulation. These controls are frequently based on sequence-specific binding of trans-acting proteins to cis-acting motifs on target RNAs. Prior studies have revealed that the KH-domain protein, alpha CP, binds to a 3' UTR C-rich motif of h alpha-globin mRNA and contributes to its cytoplasmic stability. Here, we report that this 3' UTR alpha CP complex regulates the production of mature alpha-globin mRNA by enhancing 3' processing of the h alpha-globin transcript. We go on to demonstrate that this nuclear activity reflects enhancement of both the cleavage and the polyadenylation reactions and that alpha CP interacts in vivo with core components of the 3' processing complex. Consistent with its nuclear processing activity, our studies reveal that alpha CP assembles co-transcriptionally at the h alpha-globin chromatin locus and that this loading is selectively enriched at the 3' terminus of the gene. The demonstrated linkage of nuclear processing with cytoplasmic stabilization via a common RNA-protein complex establishes a basis for integration of sequential controls critical to robust and sustained expression of a target mRNA. The EMBO Journal (2011) 30, 2622-2633. doi:10.1038/emboj.2011.171; Published online 27 May 2011