CPEB1 coordinates alternative 3′-UTR formation with translational regulation

Felice Alessio Bava, Carolina Eliscovich, Pedro G. Ferreira, Belen Miñana, Claudia Ben-Dov, Roderic Guigó, Juan Valcárcel, Raúl Méndez

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 polyadenylation 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.

Original languageEnglish (US)
Pages (from-to)121-125
Number of pages5
JournalNature
Volume494
Issue number7439
DOIs
StatePublished - Mar 7 2013

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Polyadenylation
3' Untranslated Regions
Carrier Proteins
Protein Biosynthesis
Cell Proliferation
RNA Isoforms
Messenger RNA
RNA-Binding Proteins
RNA Precursors
Alternative Splicing
Protein Binding
Carcinogenesis
Cytoplasm
Population
Genes
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Bava, F. A., Eliscovich, C., Ferreira, P. G., Miñana, B., Ben-Dov, C., Guigó, R., ... Méndez, R. (2013). CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature, 494(7439), 121-125. https://doi.org/10.1038/nature11901

CPEB1 coordinates alternative 3′-UTR formation with translational regulation. / Bava, Felice Alessio; Eliscovich, Carolina; Ferreira, Pedro G.; Miñana, Belen; Ben-Dov, Claudia; Guigó, Roderic; Valcárcel, Juan; Méndez, Raúl.

In: Nature, Vol. 494, No. 7439, 07.03.2013, p. 121-125.

Research output: Contribution to journalArticle

Bava, FA, Eliscovich, C, Ferreira, PG, Miñana, B, Ben-Dov, C, Guigó, R, Valcárcel, J & Méndez, R 2013, 'CPEB1 coordinates alternative 3′-UTR formation with translational regulation', Nature, vol. 494, no. 7439, pp. 121-125. https://doi.org/10.1038/nature11901
Bava FA, Eliscovich C, Ferreira PG, Miñana B, Ben-Dov C, Guigó R et al. CPEB1 coordinates alternative 3′-UTR formation with translational regulation. Nature. 2013 Mar 7;494(7439):121-125. https://doi.org/10.1038/nature11901
Bava, Felice Alessio ; Eliscovich, Carolina ; Ferreira, Pedro G. ; Miñana, Belen ; Ben-Dov, Claudia ; Guigó, Roderic ; Valcárcel, Juan ; Méndez, Raúl. / CPEB1 coordinates alternative 3′-UTR formation with translational regulation. In: Nature. 2013 ; Vol. 494, No. 7439. pp. 121-125.
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