The nuclear experience of CPEB: Implications for RNA processing and translational control
The nuclear experience of CPEB: Implications for RNA processing and translational control
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DOI：
10.1261/rna.1779810
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发表时间：
2010-02-01
期刊：
影响因子：
4.5
通讯作者：
Richter, Joel D.
中科院分区：
文献类型：
--
作者：
Lin, Chien-Ling;Evans, Veronica;Richter, Joel D.
CPEB是一种序列特异性RNA结合蛋白，在早期发育、细胞周期进展和细胞衰老期间以及神经元突触刺激后促进多聚腺苷酸化诱导的翻译。它通过其他相互作用分子控制多聚腺苷酸化和翻译，最值得注意的是poly（A）聚合酶Gld2、去腺苷酸化酶PARN和eIF4E结合蛋白Maskin。在这里，我们报告说，CPEB穿梭于细胞核和细胞质之间，其出口发生通过CRM1依赖性途径。在非洲爪蟾卵母细胞的核中，CPEB与灯刷染色体和参与核RNA加工的几种蛋白质相关联。CPEB还与细胞核中的Maskin以及含有CPE的mRNA相互作用。虽然CPE不调节mRNA输出，但它影响mRNA在细胞质中被抑制的程度。此外，CPEB直接或间接介导小鼠胚胎成纤维细胞以及某些小鼠组织中至少一种前mRNA的选择性剪接。我们建议，CPEB，连同Maskin，结合mRNA在细胞核中，以确保出口到细胞质后，紧密的翻译抑制。此外，我们建议，核CPEB调节特定的前mRNA选择性剪接。
CPEB is a sequence-specific RNA binding protein that promotes polyadenylation-induced translation in early development, during cell cycle progression and cellular senescence, and following neuronal synapse stimulation. It controls polyadenylation and translation through other interacting molecules, most notably the poly(A) polymerase Gld2, the deadenylating enzyme PARN, and the eIF4E-binding protein Maskin. Here, we report that CPEB shuttles between the nucleus and cytoplasm and that its export occurs via the CRM1-dependent pathway. In the nucleus of Xenopus oocytes, CPEB associates with lampbrush chromosomes and several proteins involved in nuclear RNA processing. CPEB also interacts with Maskin in the nucleus as well as with CPE-containing mRNAs. Although the CPE does not regulate mRNA export, it influences the degree to which mRNAs are translationally repressed in the cytoplasm. Moreover, CPEB directly or indirectly mediates the alternative splicing of at least one pre-mRNA in mouse embryo fibroblasts as well as certain mouse tissues. We propose that CPEB, together with Maskin, binds mRNA in the nucleus to ensure tight translational repression upon export to the cytoplasm. In addition, we propose that nuclear CPEB regulates specific pre-mRNA alternative splicing.