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

TitleELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system.
Publication TypeJournal Article
Year of Publication2015
AuthorsOktaba, K, Zhang, W, Lotz, TSabrina, Jun, DJayhyun, Lemke, SBeatrice, Ng, SPak, Esposito, E, Levine, M, Hilgers, V
JournalMol Cell
Volume57
Issue2
Pagination341-8
Date Published2015 Jan 22
ISSN1097-4164
Keywords3' Untranslated Regions, Animals, Base Sequence, Consensus Sequence, Drosophila melanogaster, Drosophila Proteins, ELAV Proteins, Genes, Insect, Polyadenylation, Promoter Regions, Genetic, Protein Binding, RNA Polymerase II, Transcription Initiation Site
Abstract

<p>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. </p>

DOI10.1016/j.molcel.2014.11.024
Alternate JournalMol. Cell
PubMed ID25544561
PubMed Central IDPMC4304968
Grant ListGM34431 / GM / NIGMS NIH HHS / United States
R01 GM034431 / GM / NIGMS NIH HHS / United States
S10RR029668 / RR / NCRR NIH HHS / United States
S10RR027303 / RR / NCRR NIH HHS / United States
S10 RR029668 / RR / NCRR NIH HHS / United States
S10 RR027303 / RR / NCRR NIH HHS / United States