Overlapping Activities of ELAV/Hu Family RNA Binding Proteins Specify the Extended Neuronal 3' UTR Landscape in Drosophila.

3' Untranslated Regions / genetics Alternative Splicing / genetics Amino Acid Motifs Animals Cell Line Cell Nucleus / metabolism Drosophila Proteins / metabolism Drosophila melanogaster / genetics ELAV Proteins / chemistry Larva / metabolism Mutation / genetics Neurons / metabolism Poly A / metabolism Protein Isoforms / metabolism RNA, Messenger / genetics
3′ UTR APA CNS Drosophila Elav Hu RBP RNA binding protein alternative polyadenylation neuron

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
01 10 2020
Historique:
received: 23 04 2020
revised: 31 07 2020
accepted: 04 09 2020
entrez: 2 10 2020
pubmed: 3 10 2020
medline: 21 10 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.molcel.2020.09.007 PMID: 33007254 PMC: PMC7546445
pubmed: 33007254
pii: S1097-2765(20)30615-8
doi: 10.1016/j.molcel.2020.09.007
pmc: PMC7546445
mid: NIHMS1629159
pii:
doi:

Substances chimiques

3' Untranslated Regions 0
Drosophila Proteins 0
ELAV Proteins 0
Protein Isoforms 0
RNA, Messenger 0
Poly A 24937-83-5

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

140-155.e6

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM083300
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083833
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

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Auteurs

Lu Wei (L)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA.

Seungjae Lee (S)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA.

Sonali Majumdar (S)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA.

Binglong Zhang (B)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA.

Piero Sanfilippo (P)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Brian Joseph (B)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA; Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Pedro Miura (P)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA; Department of Biology, University of Nevada, Reno, Reno, NV 89557, USA.

Matthias Soller (M)

School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, UK.

Eric C Lai (EC)

Department of Developmental Biology, Sloan Kettering Institute, New York, NY 10065, USA. Electronic address: laie@mskcc.org.

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Composants de gène › Régions non traduites › Régions 3' non traduites › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Maturation post-transcriptionnelle des ARN › Épissage des ARN › Épissage alternatif › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure secondaire des protéines › Motifs d'acides aminés › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Eucaryotes › Animaux › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Organites › Noyau de la cellule › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines d'arthropode › Protéines d'insecte › Protéines de Drosophila › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Pterygota › Neoptera › Holometabola › Diptera › Drosophilidae › Drosophila › Drosophila melanogaster › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Protéines à motif de reconnaissance de l'ARN › Antigènes Hu de l'encéphalomyélite paranéoplasique › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Morphogenèse › Métamorphose biologique › Étapes du cycle de vie › Larve › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Cellules › Neurones › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Polynucléotides › Polyribonucléotides › Poly A › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Isoformes de protéines › Overlapping Activities of ELAV/Hu Family RNA...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Overlapping Activities of ELAV/Hu Family RNA...