Neuronal HuD gene encoding a mRNA stability regulator is transcriptionally repressed by thyroid hormone
Open accessAbstract
Many genes governed by thyroid hormone (T3) lack binding sites for its receptor (TR) and are thought to be post‐transcriptionally regulated by T3. Here we demonstrate that the HuD gene, which encodes a neurone‐specific protein that binds to mRNA and modulates its stability, is regulated by T3. HuD RNA and protein expression were strongly up‐regulated in specific areas of the hypothyroid rat brain, and reduced by T3 in rat PC12 and mouse N2a cells containing appropriate TR levels. Furthermore, T3 inhibited the transcription of HuD in run‐on assays. Finally, HuD protein bound with high affinity to two sequences in acetylcholinesterase mRNA, and ectopic HuD expression increased its abundance in N2a cells. This is the first report of a gene encoding an mRNA stability regulator that is under T3 control. The results suggest that HuD may mediate some T3 effects by altering the half‐life of mRNAs for acetylcholinesterase and other genes.
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Prior to our study, only two transcriptional mechanisms were known to regulate expression of the HuD gene: thyroid hormone (T3) and FoxO1, and both negatively impact the abundance of HuD.
“Prior to our study, only two transcriptional mechanisms were known to regulate expression of the HuD gene—thyroid hormone (T3; presumably via activation of the thyroid hormone receptor) and TF forkhead box O1 (FoxO1)—and both of these factors were shown to negatively impact the abundance of HuD.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Cuadrado et al. 2003
In “HuD gene transcription is repressed by T3” (page not available), run-on assays show that T3 reduced HuD transcription by 60%; the paper also reports reduced HuD RNA in cells with appropriate thyroid hormone receptor levels. Our copy does not address FoxO1 or establish that these were the only two known transcriptional mechanisms. (LLM, conf=0.88)
Experimental — accuracy not yet measuredT3 decreases HuD mRNA synthesis in neuronal N2a cells, and T3 levels are inversely correlated with HuD mRNA levels in the rat brain.
“T3 was demonstrated to decrease HuD mRNA synthesis in neuronal N2a cells, and T3 levels were inversely correlated with HuD mRNA levels in the rat brain (Cuadrado et al. 2003)”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Cuadrado et al. 2003
The section ‘T3 inhibits HuD expression in PC12 and N2a cells’ reports reduced HuD RNA expression in N2a cells, while ‘HuD gene transcription is repressed by T3’ reports a reduced transcription rate without establishing that result specifically in N2a cells. The rat-brain results show higher HuD RNA under thyroid deficiency only in certain regions of the developing brain; they do not report a measured correlation between T3 and HuD mRNA levels across the rat brain. (LLM, conf=0.86)
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References 72 · Cited by 29
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- Authors
- Cuadrado, A., Navarro‐Yubero, C., Furneaux, H., & Muñoz, A.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- UConn Health (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2003-07-04
- Volume
- 86
- Issue
- 3
- Pages
- 763-773
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1642485298
- Cited by
- 29
- References
- 72
- Citations by year
- 2026: 2 · 2025: 2 · 2021: 2 · 2020: 1 · 2016: 1 · 2015: 2 · 2013: 2 · 2012: 5
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Ministerio de Ciencia y Tecnología
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- HUD, thyroid hormones, thyroid hormone receptor, mRNA stability, post-transcriptional regulation, transcriptional repression, neuronal gene expression, mRNA half-life
- MeSH terms
- Acetylcholinesterase, Animals, Base Sequence, Binding Sites, Brain, Cell Line, Gene Expression Regulation, Hypothyroidism, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Receptors, Thyroid Hormone, RNA, Messenger, Transcription, Genetic, Triiodothyronine, Blotting, Northern, Blotting, Western, RNA-Binding Proteins, PC12 Cells, Rats, Wistar, RNA Stability, Rats, ELAV Proteins
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