title: ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system.
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.
authors.affiliation: 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.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Oktaba
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Thea Sabrina
authors.initials: TS
authors.lastname: Lotz
authors.affiliation: 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.
authors.forename: David Jayhyun
authors.initials: DJ
authors.lastname: Jun
authors.affiliation: 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.
authors.forename: Sandra Beatrice
authors.initials: SB
authors.lastname: Lemke
authors.affiliation: 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.
authors.forename: Samuel Pak
authors.initials: SP
authors.lastname: Ng
authors.affiliation: 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.
authors.forename: Emilia
authors.initials: E
authors.lastname: Esposito
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Levine
authors.affiliation: 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.
authors.forename: Valérie
authors.initials: V
authors.lastname: Hilgers
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D016384:Consensus Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D051959:ELAV Proteins / Q000378:metabolism*; D017344:Genes, Insect; D026723:Polyadenylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; D051959:ELAV Proteins; C498009:ELAV protein, Drosophila; D012319:RNA Polymerase II