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Mol Cell. 2015 Jan 22;57(2):341-8. doi: 10.1016/j.molcel.2014.11.024. Epub 2014 Dec 24.

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

Author information

1
Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, Center for Integrative Genomics, University of California, Berkeley, Berkeley, CA 94720-3200, USA.
2
Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, Center for Integrative Genomics, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: mlevine@berkeley.edu.
3
Division of Genetics, Genomics and Development, Department of Molecular and Cell Biology, Center for Integrative Genomics, University of California, Berkeley, Berkeley, CA 94720-3200, USA. Electronic address: valerie.hilgers@berkeley.edu.

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.

PMID:
25544561
PMCID:
PMC4304968
DOI:
10.1016/j.molcel.2014.11.024
[Indexed for MEDLINE]
Free PMC Article

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