The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy
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After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in the superior cervical ganglion (SCG); however, the molecular events involved in this response remain unknown. Here, we first examined AChE mRNA levels in the brain of transgenic mice that overexpress human HuD. Both in situ hybridization and reverse transcription-PCR demonstrated that AChE transcript levels were increased by more than twofold in the hippocampus of HuD transgenic mice. Additionally, direct interaction between the HuD transgene product and AChE mRNA was observed. Next, we examined the role of HuD in regulating AChE expression in intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE mRNA levels resulted from changes in the stability of presynthesized transcripts. A combination of approaches performed using the region that directly encompasses an adenylate and uridylate (AU)-rich element within the AChE 3'-untranslated region demonstrated a decrease in RNA-protein complexes in response to axotomy of the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD transcript and protein levels also decreased. Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy. Together, the results of this study demonstrate that AChE expression in neurons of the rat SCG is regulated via post-transcriptional mechanisms that involve the AU-rich element and HuD.
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Between 1 and 4 d following axotomy of superior cervical ganglion (SCG) neurons, HuD protein and mRNA levels, its interaction with AChE mRNA, and AChE transcript levels decreased.
“A study in our laboratory demonstrated that, between 1 and 4 d following axotomy of superior cervical ganglion (SCG) neurons, HuD protein and mRNA levels, its interaction with AChE mRNA, and AChE transcript levels decreased (Deschenes-Furry et al. 2007).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Deschenes-Furry et al. 2007
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Holahan, M. R. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00266 · Cited by 197 · see citing works
RNA–protein interactions and control of mRNA stability in neurons
Bolognani, F., & Perrone‐Bizzozero, N. I. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21473 · Cited by 196 · see citing works
Self-citationHubers, L., Valderrama-Carvajal, H., Laframboise, J., Timbers, J., Sanchez, G., & Côté, J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddq500 · Cited by 138 · see citing works
Bronicki, L. M., & Jasmin, B. J. (2013) · RNA · doi:10.1261/rna.039164.113 · Cited by 126 · see citing works
Self-citationDegradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1
Sosanya, N. M., Huang, P. P. C., Cacheaux, L. P., Chen, C. J., Nguyen, K., Perrone-Bizzozero, N. I., & Raab-Graham, K. F. (2013) · Journal of Cell Biology · doi:10.1083/jcb.201212089 · Cited by 117 · see citing works
Self-citationBolognani, F., Contente-Cuomo, T., & Perrone-Bizzozero, N. I. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp863 · Cited by 113 · see citing works
Self-citationRNA-Binding Protein FXR2 Regulates Adult Hippocampal Neurogenesis by Reducing Noggin Expression
Guo, W., Zhang, L., Christopher, D. M., Teng, Z., Fausett, S. R., Liu, C.-M., George, O. L., Klingensmith, J., Jin, P., & Zhao, X. (2011) · Neuron · doi:10.1016/j.neuron.2011.03.027 · Cited by 96 · see citing works
Tebaldi, T., Zuccotti, P., Peroni, D., Köhn, M., Gasperini, L., Potrich, V., Bonazza, V., Dudnakova, T., Rossi, A., Sanguinetti, G., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.032 · Cited by 59 · see citing works
Activity‐dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain
Tiruchinapalli, D. M., Caron, M. G., & Keene, J. D. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05718.x · Cited by 53 · see citing works
Role of HuD in nervous system function and pathology
Perrone‐Bizzozero, N. I. (2012) · Frontiers in Bioscience-Scholar · doi:10.2741/s389 · Cited by 52 · see citing works
Self-citationHuD-mediated distinct BDNF regulatory pathways promote regeneration after nerve injury
Sanna, M. D., Ghelardini, C., & Galeotti, N. (2017) · Brain Research · doi:10.1016/j.brainres.2017.01.019 · Cited by 48 · see citing works
GAP-43 in synaptic plasticity: molecular perspectives
Holahan, M. R. (2015) · Research and Reports in Biochemistry · doi:10.2147/rrbc.s73846 · Cited by 42 · see citing works
PKC-mediated HuD–GAP43 pathway activation in a mouse model of antiretroviral painful neuropathy
Sanna, M. D., Quattrone, A., Ghelardini, C., & Galeotti, N. (2014) · Pharmacological Research · doi:10.1016/j.phrs.2014.02.004 · Cited by 42 · see citing works
Bolognani, F., Tanner, D. C., Nixon, S., Okano, H. J., Okano, H., & Perrone‐Bizzozero, N. I. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9388-8 · Cited by 42 · see citing works
Self-citationRNA–Binding Protein HuD as a Versatile Factor in Neuronal and Non–Neuronal Systems
Jung, M., & Lee, E. K. (2021) · Biology · doi:10.3390/biology10050361 · Cited by 39 · see citing works
van der Linden, R. J., Gerritsen, J. S., Liao, M., Widomska, J., Pearse, R. V., White, F. M., Franke, B., Young‐Pearse, T. L., & Poelmans, G. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102316 · Cited by 40 · see citing works
Merino, P., Díaz, A., Torre, E. R., & Yepes, M. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010644 · Cited by 30 · see citing works
Xie, H. Q., Choi, R. C. Y., Leung, K. W., Chen, V. P., Chu, G. K. Y., & Tsim, K. W. K. (2009) · Brain Research · doi:10.1016/j.brainres.2009.01.065 · Cited by 30 · see citing works
Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
Silvestri, B., Mochi, M., Garone, M. G., & Rosa, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314606 · Cited by 28 · see citing works
Perrone‐Bizzozero, N. I., Tanner, D. C., Mounce, J., & Bolognani, F. (2011) · ASN NEURO · doi:10.1042/an20110015 · Cited by 26 · see citing works
Self-citationSanna, M. D., Quattrone, A., Mello, T., Ghelardini, C., & Galeotti, N. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.05.017 · Cited by 24 · see citing works
HuD Regulates the cpg15 Expression Via the 3′-UTR and AU-Rich Element
Wang, Z., Li, S.-J., Qi, Y., Zhao, J., Liu, X.-Y., Han, Y., Xu, P., & Chen, X.-H. (2011) · Neurochemical Research · doi:10.1007/s11064-011-0443-0 · Cited by 23 · see citing works
Leautaud, V., & Demple, B. (2007) · BMC Molecular Biology · doi:10.1186/1471-2199-8-116 · Cited by 22 · see citing works
Roles of Embryonic Lethal Abnormal Vision-Like RNA Binding Proteins in Cancer and Beyond
Cai, H., Zheng, D., Yao, Y., Yang, L., Huang, X., & Wang, L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.847761 · Cited by 18 · see citing works
Trans-acting factors governing acetylcholinesterase mRNA metabolism in neurons
Bronicki, L., & Jasmin, B. J. (2012) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2012.00036 · Cited by 14 · see citing works
Self-citationBronicki, L., Bélanger, G., & Jasmin, B. J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.2247-12.2012 · Cited by 13 · see citing works
Self-citationInjury-induced gp130 cytokine signaling in peripheral ganglia is reduced in diabetes mellitus
Niemi, J. P., Filous, A. R., Oranburg, T. D., Lindborg, J. A., Malhotra, N. A., Wilson, G. N., Zhou, B., Crish, S. D., & Zigmond, R. E. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.06.020 · Cited by 13 · see citing works
Motor Neuron Biology and Disease: A Current Perspective on Infantile-Onset Spinal Muscular Atrophy
Jha, N. N., Kim, J.-K., & Monani, U. R. (2018) · Future Neurology · doi:10.2217/fnl-2018-0008 · Cited by 13 · see citing works
Wild‐type and mutant SOD1 localizes to RNA‐rich structures in cells and mice but does not bind RNA
Ros, M. D., Deol, H. K., Savard, A., Guo, H., Meiering, E. M., & Gibbings, D. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15126 · Cited by 12 · see citing works
Identification of autoantigens in pediatric opsoclonus-myoclonus syndrome
Blaes, F., Fühlhuber, V., & Preissner, K. T. (2007) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.3.6.975 · Cited by 12 · see citing works
Cardoso, J. D. S., Baldissarelli, J., Reichert, K. P., Teixeira, F. C., Soares, M. S. P., Schetinger, M. R. C., Morsch, V. M., Filho, A. O. F. M., Duarte, H. R., Coriolano, F. H. R., et al. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111157 · Cited by 10 · see citing works
Application of Serum ELAVL4 (HuD) Antigen Assay for Small Cell Lung Cancer Diagnosis
WANG, F., LU, J., Li, S., Huo, X., Liu, X., Du, X., Li, C., Wang, J., & Chen, Z. (2017) · Anticancer Research · doi:10.21873/anticanres.11848 · Cited by 10 · see citing works
Identification of cis-acting elements involved in Acetylcholinesterase RNA alternative splicing
Guerra, M., Dobbertin, A., & Legay, C. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.01.007 · Cited by 9 · see citing works
Aberrant translation of proteins implicated in Alzheimer�s disease pathology
Bottley, A., & Kondrashov, A. (2013) · OA Genetics · doi:10.13172/2054-197x-1-1-918 · Cited by 2 · see citing works
HuD Regulates the cpg15 Expression Via the 3 0 -UTR and AU-Rich Element
WangShu-Jing, Z.-H., Qi, L., & Han, L. (2011) · Cited by 1 · see citing works
Bird, C. W. (2012) · UNM’s Digital Repository (University of New Mexico)
Protein Predictors of Worsening Cerebral Edema in Traumatic Brain Injury in Critically Ill PatientsPreprint
Radabaugh, H. L., Abdelhak, A., Ning, K., Jha, R. M., Rowell, S., Pollock, J. M., Mendoza, E., Rojas-Valencia, L. M., Ferguson, A. R., & Hinson, H. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.23.727416
Bishayee, K., Kaviarasan, V., Yoo, S. Y., Lee, S. H., & Park, Y. S. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177882
ELAVL Proteins, miRNA Fate, and Extracellular RNA Communication in Brain Aging and Neurodegeneration
Mukherjee, K., & Bhattacharyya, S. N. (2026) · Cells · doi:10.3390/cells15181649
Circulating Exosomes Drive Persistent Neuronal Dysfunction in Post‐Herpetic Neuralgia Patients
Niemeyer, C. S., Frietze, S. E., Lewis, S. W. R., Artman, E. C., Coughlan, C. M., Vaseemuddin, S. I., Polese, A. G., Nagel, M. A., Tyring, S. K., Okundia, F., et al. (2026) · Annals of Neurology · doi:10.1002/ana.78352
- Authors
- Deschênes-Furry, J., Mousavi, K., Bolognani, F., Neve, R. L., Parks, R. J., Perrone-Bizzozero, N. I., & Jasmin, B. J.
- Affiliations
- University of Ottawa (CA)
- Harvard University (US)
- Ottawa Hospital (CA)
- Corresponding author
- Jasmin, Bernard J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-17
- Volume
- 27
- Issue
- 3
- Pages
- 665-675
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672799
- OpenAlex
- W1977621096
- Cited by
- 43
- References
- 98
- Citations by year
- 2026: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 4 · 2015: 1 · 2014: 2 · 2013: 5 · 2012: 4
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke (NS 30255, R01NS030255)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- HUD, RNA-binding proteins, acetylcholinesterase, mRNA stability, axotomy, superior cervical ganglion, AU-rich elements, post-transcriptional regulation, GAP-43, neuronal gene expression, hippocampus, protein-RNA complex
- MeSH terms
- ELAV-Like Protein 4, Acetylcholinesterase, Animals, Female, Humans, Mice, Transgenic, Neurons, Protein Binding, RNA, Messenger, Gene Expression Regulation, Enzymologic, RNA-Binding Proteins, Rats, Sprague-Dawley, Superior Cervical Ganglion, Axotomy, Mice, Rats, ELAV Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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