Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3′ UTR landscape in drosophila Journal Article

Authors: Wei, L.; Lee, S.; Majumdar, S.; Zhang, B.; Sanfilippo, P.; Joseph, B.; Miura, P.; Soller, M.; Lai, E. C.
Article Title: Overlapping activities of ELAV/Hu family RNA binding proteins specify the extended neuronal 3′ UTR landscape in drosophila
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. © 2020 Elsevier Inc. Neurons express much longer 3′ UTRs than other cell types. Here, Wei and Lee et al. determine that overlapping roles of Drosophila ELAV/Hu RNA binding proteins are necessary and sufficient to determine the extended 3′ UTR landscape. Moreover, their compensatory functions involve splicing and subcellular regulation between ELAV/Hu members. © 2020 Elsevier Inc.
Keywords: controlled study; unclassified drug; genetics; mutation; nonhuman; protein localization; protein motif; animal; metabolism; animals; gene expression; embryo; cell line; drosophila; neurons; wild type; central nervous system; rna binding protein; chemistry; messenger rna; rna, messenger; chromatin; alternative splicing; alternative rna splicing; down regulation; 3' untranslated region; drosophila melanogaster; cell nucleus; nerve cell; drosophila proteins; transcriptome; hu protein; isoprotein; protein isoforms; amino acid motifs; drosophila protein; larva; 3' untranslated regions; northern blotting; cns; lamin c; polyadenylation; polyadenylic acid; alternative polyadenylation; article; rna sequencing; 3′ utr; poly a; apa; genetic background; neuron; hu; elav proteins; elav; elav protein; rbp; rna binding protein 9; rna binding protein fne
Journal Title: Molecular Cell
Volume: 80
Issue: 1
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2020-10-01
Start Page: 140
End Page: 155.e6
Language: English
DOI: 10.1016/j.molcel.2020.09.007
PUBMED: 33007254
PROVIDER: scopus
PMCID: PMC7546445
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Eric C Lai
    141 Lai
  2. Pedro Edward Taiyo Miura
    6 Miura
  3. Brian Jude Joseph
    9 Joseph
  4. Binglong Zhang
    5 Zhang
  5. Lu Wei
    3 Wei
  6. Seungjae Lee
    4 Lee