ELAV links paused pol II to alternative polyadenylation in the drosophila nervous system

Katarzyna Oktaba, Wei Zhang, Thea Sabrina Lotz, David Jayhyun Jun, Sandra Beatrice Lemke, Samuel Pak Ng, Emilia Esposito, Michael Levine, Valérie Hilgers

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Alternative polyadenylation (APA) has been implicated in a variety of developmental and disease processes. A particularly dramatic form of APA occurs inthe 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.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalMolecular Cell
Volume57
Issue number2
DOIs
StatePublished - Jan 22 2015

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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