Cited by 156RNA Research and SplicingRNA regulation and diseaseCell death mechanisms and regulation

Hu Antigen R (HuR) Functions as an Alternative Pre-mRNA Splicing Regulator of Fas Apoptosis-promoting Receptor on Exon Definition

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Izquierdo, José M.·2008·Journal of Biological Chemistry

Abstract

Exclusion of exon 6 by alternative RNA splicing of the primary transcript of the apoptosis receptor Fas produces a soluble isoform that prevents programmed cell death. I report that antiapoptotic regulator Hu antigen R (HuR, ELAVL1), a member of the embryonic lethal, abnormal vision, Drosophila-like (ELAVL) family, promotes Fas exon 6 skipping by binding to an exonic splicing silencer. HuR inhibits the association of U2 small nuclear ribonucleoprotein (snRNP) auxiliary factor 65 kDa (U2AF65) with the upstream 3' splice site, without decreasing recognition of the downstream 5' splice site by U1 snRNP but by antagonizing the role of TIA-1 (T-cell intracellular antigen 1)/TIAR (TIA-1 related protein) on exon definition. Remarkably, U1 snRNP-mediated recognition of the 5' splice site is partially required for efficient U2AF65 inhibition. Further, the silencing capacity of HuR as splicing regulator resides in the RRM1 and hinge-RRM3 domains. Taken together, these results support a functional link between HuR as repressor of alternative Fas splicing and the molecular mechanisms modulating programmed cell death.

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Crossref · 10.1074/jbc.m800017200

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Authors
Izquierdo, J. M.
Affiliations
Centro de Biología Molecular Severo Ochoa (ES)
Corresponding author
Izquierdo, José M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2008-07
Volume
283
Issue
27
Pages
19077-19084
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1973614363
Cited by
156
References
45
Citations by year
2026: 2 · 2025: 5 · 2024: 7 · 2023: 11 · 2022: 11 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 15 · 2014: 15 · 2013: 15 · 2012: 5
FWCI
3.69
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
HuR, Fas, alternative splicing, exonic splicing silencer, U2AF65, U1 snRNP, TIA-1, TIAR, exon definition, programmed cell death, apoptosis, RRM1 domain, splicing repressor
MeSH terms
ELAV-Like Protein 1, Splicing Factor U2AF, T-Cell Intracellular Antigen-1, Animals, Antigens, Surface, Drosophila melanogaster, Exons, HeLa Cells, Humans, Nuclear Proteins, Ribonucleoproteins, Ribonucleoside Diphosphate Reductase, RNA Precursors, RNA-Binding Proteins, Apoptosis, Alternative Splicing, Ribonucleoprotein, U1 Small Nuclear, Ribonucleoprotein, U2 Small Nuclear, Protein Structure, Tertiary, fas Receptor, RNA Splice Sites, Tumor Suppressor Proteins, Poly(A)-Binding Proteins, ELAV Proteins

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