The ELAV Protein HuD Stimulates Cap-Dependent Translation in a Poly(A)- and eIF4A-Dependent Manner
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The RNA-binding protein HuD promotes neuronal differentiation by an unknown mechanism. Here we identify an enhancer function of HuD in translation. Translation stimulation by HuD requires both a 3' poly(A) tail and a 5' m(7)G cap structure. We also show that HuD directly interacts with eIF4A. This interaction and the poly(A)-binding activity of HuD are critical for its translational enhancer function because HuD-eIF4A- and HuD-poly(A)-binding mutants fail to stimulate translation. We show that translation of HCV IRES mRNA, which is eIF4A independent, is not stimulated by HuD. We also find that the eIF4A and poly(A)-binding activities of HuD are not only important for stimulating translation but also are essential for HuD-induced neurite outgrowth in PC12 cells. This example of cap-dependent translational regulation might explain at least in part how HuD triggers the induction of neuronal differentiation.
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This mechanism is important for HuD-dependent neurite extension in PC12 cells.
“Moreover, this mechanism was determined to be important for HuD- dependent neurite extension in PC12 cells.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Fukao et al. 2009
HuD binds to eIF4A and the poly(A) tail of transcripts, via its linker region and third RRM, to enhance cap-dependent protein synthesis.
“Complementary to its role in mRNA localization, evidence for the direct involvement of HuD in regulating translation was unveiled when Fukao and colleagues showed that HuD binds to eIF4A and the poly(A) tail of transcripts, via its linker region and third RRM, to enhance cap-dependent protein synthesis (Fukao et al. 2009).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Fukao et al. 2009
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References 53 · Cited by 100
- Authors
- Fukao, A., Sasano, Y., Imataka, H., Inoue, K., Sakamoto, H., Sonenberg, N., Thoma, C., & Fujiwara, T.
- Affiliations
- Kobe University (JP)
- Nagase (Japan) (JP)
- University of Hyogo (JP)
- McGill University (CA)
- University Medical Center Freiburg (DE)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Thoma, Christian
- Fujiwara, Toshinobu
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 36
- Issue
- 6
- Pages
- 1007-1017
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2044583310
- Cited by
- 100
- References
- 53
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 7
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft
- Total Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Social Sciences › Arts and Humanities › Language and Linguistics › Translation Studies and Practices
- Keywords
- HUD, cap-dependent translation, poly(A) tail, eIF4A, translational enhancer, neuronal differentiation, neurite outgrowth, RNA-binding proteins, PC12 cells
- MeSH terms
- ELAV-Like Protein 4, Amino Acid Sequence, Animals, Enhancer Elements, Genetic, HeLa Cells, Humans, Molecular Sequence Data, Neurons, Recombinant Fusion Proteins, RNA Caps, RNA, Messenger, Protein Biosynthesis, PC12 Cells, Eukaryotic Initiation Factor-4A, Mice, Rats, ELAV Proteins
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