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CPEB1 coordinates alternative 3'-UTR formation with translational regulation

机译：CPEB1通过翻译调控来协调3'-UTR的形成

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摘要

CPEB1(一种RNA结合蛋白，与信使RNA 3'-rnUTR多腺苷酸化序列发生相互作用)已知调控rn细胞质的多腺苷酸化。Raul Merldez及其同事rn介绍了它在细胞核中的第二种功能。在细胞核rn中，CPEB1与剪接因子共同作用，促进很多rnmRNA中一个上游3'poly(A)信号的使用，影rn响另类剪接。因为poly(A)尾巴的缩短已被与rn增殖和肿瘤发生联系起来，所以这些结果为这rn一变化是怎样通过由CPEB1将另类多腺苷酸rn化和另类剪接联系起来实现的提供了一个解rn释。这种双重功能(即作为翻译调控因子的功rn能和作为pre-mRNA处理因子的功能)也许意味rn着，CPEB1能够协调细胞核和细胞质的基因rn表达调控。%More than half of mammalian genes generate multiple messenger RNA isoforms that differ in their 3' untranslated regions (3' UTRs) and therefore in regulatory sequences, often associated with cell proliferation and cancer; however, the mechanisms coordinating alternative 3'-UTR processing for specific mRNA populations remain poorly defined. Here we report that the cytoplasmic poly-adenylation element binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation, also controls alternative 3'-UTR processing. CPEB1 shuttles to the nucleus, where it co-localizes with splicing factors and mediates shortening of hundreds of mRNA 3' UTRs, thereby modulating their translation efficiency in the cytoplasm. CPEB1-mediated 3'-UTR shortening correlates with cell proliferation and tumorigenesis. CPEB1 binding to pre-mRNAs not only directs the use of alternative polyadenylation sites, but also changes alternative splicing by preventing U2AF65 recruitment. Our results reveal a novel function of CPEB1 in mediating alternative 3'-UTR processing, which is coordinated with regulation of mRNA translation, through its dual nuclear and cytoplasmic functions.
机译：CPEB1(一种RNA结合蛋白，与信使RNA 3'-rnUTR多腺苷酸化序列发生相互作用)已知调控rn细胞质的多腺苷酸化。Raul Merldez及其同事rn介绍了它在细胞核中的第二种功能。在细胞核rn中，CPEB1与剪接因子共同作用，促进很多rnmRNA中一个上游3'poly(A)信号的使用，影rn响另类剪接。因为poly(A)尾巴的缩短已被与rn增殖和肿瘤发生联系起来，所以这些结果为这rn一变化是怎样通过由CPEB1将另类多腺苷酸rn化和另类剪接联系起来实现的提供了一个解rn释。这种双重功能(即作为翻译调控因子的功rn能和作为pre-mRNA处理因子的功能)也许意味rn着，CPEB1能够协调细胞核和细胞质的基因rn表达调控。%More than half of mammalian genes generate multiple messenger RNA isoforms that differ in their 3' untranslated regions (3' UTRs) and therefore in regulatory sequences, often associated with cell proliferation and cancer; however, the mechanisms coordinating alternative 3'-UTR processing for specific mRNA populations remain poorly defined. Here we report that the cytoplasmic poly-adenylation element binding protein 1 (CPEB1), an RNA-binding protein that regulates mRNA translation, also controls alternative 3'-UTR processing. CPEB1 shuttles to the nucleus, where it co-localizes with splicing factors and mediates shortening of hundreds of mRNA 3' UTRs, thereby modulating their translation efficiency in the cytoplasm. CPEB1-mediated 3'-UTR shortening correlates with cell proliferation and tumorigenesis. CPEB1 binding to pre-mRNAs not only directs the use of alternative polyadenylation sites, but also changes alternative splicing by preventing U2AF65 recruitment. Our results reveal a novel function of CPEB1 in mediating alternative 3'-UTR processing, which is coordinated with regulation of mRNA translation, through its dual nuclear and cytoplasmic functions.

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  • 来源
    《Nature》 |2013年第7439期|121-125B2|共6页
  • 作者

    Felice-Alessio Bava; Carolina Eliscovich; Pedro G. Ferreira; Belen Minana; Claudia Ben-Dov; Roderic Guigo; Juan Valcarcel; Raul Mendez;

  • 作者单位

    Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10,08028 Barcelona, Spain;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain,Albert Einstein College of Medicine, Departmentof Anatomy and Structural Biology, Bronx, New York 10461, USA;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain;

    Centre for Genomic Regulation (CRG), UPF, Dr. Aiguader 88,08003 Barcelona, Spain,lnstitucio Catalana de Recercai Estudis Avancats(ICREA), Passeig Lluis companys 23, Barcelona, 08010, Spain;

    Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10,08028 Barcelona, Spain,lnstitucio Catalana de Recercai Estudis Avancats(ICREA), Passeig Lluis companys 23, Barcelona, 08010, Spain;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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