Post-transcriptional Regulation of Acetylcholinesterase mRNAs in Nerve Growth Factor-treated PC12 Cells by the RNA-binding Protein HuD
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Expression of acetylcholinesterase (AChE) is greatly enhanced during neuronal differentiation, but the nature of the molecular mechanisms remains to be fully defined. In this study, we observed that nerve growth factor treatment of PC12 cells leads to a progressive increase in the expression of AChE transcripts, reaching approximately 3.5-fold by 72 h. Given that the AChE 3'-untranslated region (UTR) contains an AU-rich element, we focused on the potential role of the RNA-binding protein HuD in mediating the increase in AChE mRNA seen in differentiating neurons. Using PC12 cells engineered to stably express HuD or an antisense to HuD, our studies indicate that HuD can regulate the abundance of AChE transcripts in neuronal cells. Furthermore, transfection of a reporter construct containing the AChE 3'-UTR showed that this 3'-UTR can increase expression of the reporter gene product in cells expressing HuD but not in cells expressing the antisense. RNA gel shifts and Northwestern blots revealed an increase in the binding of several protein complexes in differentiated neurons. Immunoprecipitation experiments demonstrated that HuD can bind directly AChE transcripts. These results show the importance of post-transcriptional mechanisms in regulating AChE expression in differentiating neurons and implicate HuD as a key trans-acting factor in these events.
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HuD promotes the stability of AChE and Nova1 mRNAs in vitro and in vivo.
“In addition to GAP-43 transcripts, HuD has also been shown to promote the stability of several other ARE-containing mRNAs in neurons, such as AChE (Deschenes-Furry et al. 2003) and Nova1 (Ratti et al. 2008), both in vitro and in vivo (Table 2; Perrone-Bizzozero and Bird 2013).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Deschenes-Furry et al. 2003
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References 80 · Cited by 65
Research works printed but not linked: 2
- Hammond, P., Rao, R., Koenigsberger, C., and Brimijoin, S. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 10933-10937
- Chan, R. Y., Boudreau-Lariviere, C., Angus, L. M., Mankal, F. A., and Jasmin, B. J. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 4627-4632
- Authors
- Deschênes-Furry, J., Bélanger, G., Perrone-Bizzozero, N., & Jasmin, B. J.
- Affiliations
- University of Ottawa (CA)
- Corresponding author
- Jasmin, Bernard J.
- ORCID
- Jasmin, Bernard J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 278
- Issue
- 8
- Pages
- 5710-5717
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2035618537
- Cited by
- 65
- References
- 80
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2014: 2 · 2013: 3 · 2012: 5
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ontario Neurotrauma Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke (NS 30255)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- acetylcholinesterase, HUD, RNA-binding proteins, post-transcriptional regulation, mRNA stability, AU-rich elements, 3' untranslated region, nerve growth factor, neuronal differentiation, PC12 cells, trans-acting factors
- MeSH terms
- ELAV-Like Protein 4, Acetylcholinesterase, Animals, Base Sequence, Humans, Kinetics, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Pheochromocytoma, RNA Processing, Post-Transcriptional, RNA, Messenger, Sequence Homology, Nucleic Acid, Transcription, Genetic, Transfection, Gene Expression Regulation, Enzymologic, Sequence Alignment, RNA-Binding Proteins, PC12 Cells, Genes, Reporter, Nerve Growth Factor, Mice, Rats, ELAV Proteins
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