Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs
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The messenger RNAs of many proto-oncogenes, cytokines and lymphokines are targeted for rapid degradation through AU-rich elements (AREs) located in their 3' untranslated regions (UTRs). HuR, a ubiquitously expressed member of the Elav family of RNA binding proteins, exhibits specific affinities for ARE-containing RNA sequences in vitro which correlate with their in vivo decay rates, thereby implicating HuR in the ARE-mediated degradation pathway. We have transiently transfected HuR into mouse L929 cells and observed that overexpression of HuR enhances the stability of beta-globin reporter mRNAs containing either class I or class II AREs. The increase in mRNA stability parallels the level of HuR overexpression, establishing an in vivo role for HuR in mRNA decay. Furthermore, overexpression of HuR deletion mutants lacking RNA recognition motif 3 (RRM 3) does not exert a stabilizing effect, indicating that RRM 3 is important for HuR function. We have also developed polyclonal anti-HuR antibodies. Immunofluorescent staining of HeLa and L929 cells using affinity-purified anti-HuR antibody shows that both endogenous and overexpressed HuR proteins are localized in the nucleus. By forming HeLa-L929 cell heterokaryons, we demonstrate that HuR shuttles between the nucleus and cytoplasm. Thus, HuR may initially bind to ARE-containing mRNAs in the nucleus and provide protection during and after their export to the cytoplasmic compartment.
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Prototype foamy virus achieves nuclear export of its unspliced RNA by interacting with HuR, a ubiquitously expressed nuclear RNA-binding shuttle protein involved in nuclear export of AU-rich elements-containing cellular mRNAs.
“The prototype foamy virus achieves nuclear export of its unspliced RNA by interacting with human antigen R (HuR), a ubiquitously expressed nuclear RNA-binding shuttle protein known to be involved in the nuclear export of AU-rich elements-containing cellular mRNAs (Fig. 9) (Fan and Steitz 1998, Bodem et al. 2011).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Fan and Steitz 1998
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“9 ) (Fan and Steitz 1998 , Bodem et al. 2011 ).”
- Authors
- Fan, X. C., & Steitz, J. A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Steitz, Joan A.
- Venue
- The EMBO Journal
- Published
- 1998-06-15
- Volume
- 17
- Issue
- 12
- Pages
- 3448-3460
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170681
- OpenAlex
- W2096259566
- Cited by
- 866
- References
- 2
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 13 · 2023: 21 · 2022: 19 · 2021: 22 · 2020: 19 · 2019: 27 · 2018: 25 · 2017: 13 · 2016: 19 · 2015: 30 · 2014: 19 · 2013: 37 · 2012: 42
- FWCI
- 15.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA1 6038)
- National Cancer Institute (CA-16038, P01CA016038)
- 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 › RNA and protein synthesis mechanisms
- Keywords
- HuR, AU-rich elements, mRNA stability, mRNA degradation, 3' untranslated region, nucleocytoplasmic shuttling, beta-globin mRNA, L929 fibroblasts
- MeSH terms
- ELAV-Like Protein 1, Animals, Antigens, Surface, Cell Nucleus, Cells, Cultured, Cytoplasm, HeLa Cells, Humans, RNA, Messenger, RNA-Binding Proteins, Mice, ELAV Proteins
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