Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3' UTR landscape in Drosophila

Lu Wei, Seungjae Lee, Sonali Majumdar, Binglong Zhang, Piero Sanfilippo, Brian Joseph, Pedro Miura, Matthias Soller, Eric Lai

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
27 Downloads (Pure)

Abstract

The tissue-specific deployment of highly extended neural 3′ UTR isoforms, generated by alternative polyadenylation (APA), is a broad and conserved feature of metazoan genomes. However, the factors and mechanisms that control neural APA isoforms are not well understood. Here, we show that three ELAV/Hu RNA binding proteins (Elav, Rbp9, and Fne) have similar capacities to induce a lengthened 3′ UTR landscape in an ectopic setting. These factors promote accumulation of chromatin-associated, 3′ UTR-extended, nascent transcripts, through inhibition of proximal polyadenylation site (PAS) usage. Notably, Elav represses an unannotated splice isoform of fne, switching the normally cytoplasmic Fne toward the nucleus in elav mutants. We use genomic profiling to reveal strong and broad loss of neural APA in elav/fne double mutant CNS, the first genetic background to largely abrogate this distinct APA signature. Overall, we demonstrate how regulatory interplay and functionally overlapping activities of neural ELAV/Hu RBPs drives the neural APA landscape.

Original languageEnglish
Pages (from-to)140-155.e6
Number of pages23
JournalMolecular Cell
Volume80
Issue number1
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • 3′ UTR
  • APA
  • CNS
  • Drosophila
  • Elav
  • Hu
  • RBP
  • RNA binding protein
  • alternative polyadenylation
  • neuron

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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