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ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system

Author(s): Oktaba, Katarzyna; Zhang, Wei; Lotz, Thea Sabrina; Jun, David Jayhyun; Lemke, Sandra Beatrice; et al

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Abstract: Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes. A particularly dramatic form of APA occurs in the developing nervous system of flies and mammals, whereby various developmental genes undergo coordinate 3' UTR extension. In Drosophila, the RNA-binding protein ELAV inhibits RNA processing at proximal polyadenylation sites, thereby fostering the formation of exceptionally long 3' UTRs. Here, we present evidence that paused Pol II promotes recruitment of ELAV to extended genes. Replacing promoters of extended genes with heterologous promoters blocks normal 3' extension in the nervous system, while extension-associated promoters can induce 3' extension in ectopic tissues expressing ELAV. Computational analyses suggest that promoter regions of extended genes tend to contain paused Pol II and associated cis-regulatory elements such as GAGA. ChIP-seq assays identify ELAV in the promoter regions of extended genes. Our study provides evidence for a regulatory link between promoter-proximal pausing and APA.
Publication Date: 22-Jan-2015
Citation: Oktaba, Katarzyna, Zhang, Wei, Lotz, Thea Sabrina, Jun, David Jayhyun, Lemke, Sandra Beatrice, Ng, Samuel Pak, Esposito, Emilia, Levine, Michael, Hilgers, Valérie. (2015). ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system. Molecular Cell, 57 (2), 341 - 348. doi:10.1016/j.molcel.2014.11.024
DOI: doi:10.1016/j.molcel.2014.11.024
ISSN: 1097-2765
EISSN: 1097-4164
Pages: 341 - 348
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Molecular Cell
Version: Author's manuscript

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