Embryonic Lethal Abnormal Vision-Like RNA-Binding Proteins Regulate Neurite Outgrowth and Tau Expression in PC12 Cells
Open accessAbstract
The embryonic lethal abnormal vision (ELAV)-like proteins are mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family are required for neuronal differentiation. We identified the binding region of purified HuD protein to a target neuronal mRNA encoding for the tau microtubule-associated protein and demonstrated an in vivo interaction between the ELAV-like protein and its target tau mRNA. We show that treatment of neuronal cells with antisense oligodeoxynucleotides directed against HuD blocks the induction of neurite outgrowth and decreases the levels of tau mRNAs, indicating that the ELAV-like proteins are required for neuronal differentiation.
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In developing neurons, HuD is found in growth cones of extending neurites, while in mature neurons it is present in axons and dendrites, including at the pre- and post-neurite terminals.
“In developing neurons, HuD is found in growth cones of extending neurites, while in mature neurons it is present in axons and dendrites, including at the pre- and post-neurite terminals, respectively (Aranda-Abreu et al. 1999; Aronov et al. 2002).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aranda-Abreu et al. 1999
The Results section, “The ELAV-like protein–tau mRNA complex is associated with microtubules in vivo” (page not provided), reports ELAV-like protein staining extending into neurites and growth cones of NGF-treated PC12 cells. It does not establish that the staining is specifically HuD, or describe HuD in the axons, dendrites, or pre- and post-neurite terminals of mature neurons. (LLM, conf=0.85)
Experimental — accuracy not yet measuredHuD has an essential role in terminal differentiation, namely dendritic and axonal outgrowth.
“Studies in which HuD levels were down-regulated or over-expressed in cultured cells have revealed an essential role for HuD in terminal differentiation, namely dendritic and axonal outgrowth (Wakamatsu and Weston 1997; Aranda-Abreu et al. 1999; Mobarak et al. 2000; Anderson et al. 2001; Hubers et al. 2010).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aranda-Abreu et al. 1999
The section on r-HuD antisense treatment reports that reducing HuD caused neurite retraction in NGF-treated PC12 cells, supporting a role in neurite outgrowth. The Discussion explicitly says this model produces neurite extension, not defined dendrites and axons, so this paper does not establish the claim's more specific dendritic and axonal outgrowth. Page numbers were not provided for these passages. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThis function of HuD requires its shuttling to the cytoplasm and involves stabilization of various target mRNAs whose protein products promote microtubule assembly and growth cone development including GAP-43, Tau, and AChE.
“This function of HuD requires its shuttling to the cytoplasm and involves stabilization of various target mRNAs whose protein products promote microtubule assembly and growth cone development including GAP-43, Tau, and AChE (Chung et al. 1997; Aranda-Abreu et al. 1999; Kasashima et al. 1999; Deschenes-Furry et al. 2003).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aranda-Abreu et al. 1999
The ‘Characterization of HuD–tau mRNA complex formation’ section shows that HuD binds tau mRNA, and the antisense-treatment results link reduced HuD to reduced tau mRNA and protein in PC12 cells. The Discussion treats tau mRNA stabilization as a possible mechanism but says how ELAV-like proteins control mRNA half-life remains undetermined. These passages do not establish that HuD must shuttle to the cytoplasm or that this paper demonstrates stabilization of GAP-43 and AChE mRNAs. Page numbers were unavailable in the indexed passages. (LLM, conf=0.86)
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“The human members of the family (HuD, Hel-N1, HuC, and HuR) are of particular interest because they were independently discovered as tumor antigens (Szabo et al., 1991; Sakai et al., 1994).”
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- Authors
- Aranda-Abreu, G. E., Behar, L., Chung, S., Furneaux, H., & Ginzburg, I.
- Affiliations
- Weizmann Institute of Science (IL)
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-08-15
- Volume
- 19
- Issue
- 16
- Pages
- 6907-6917
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782881
- OpenAlex
- W2142664254
- Cited by
- 142
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 8 · 2012: 3
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9604175)
- Israel Academy of Sciences and Humanities
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ELAV-like proteins, HUD, RNA-binding proteins, mRNA stability, tau protein, neurite outgrowth, neuronal differentiation, antisense oligodeoxynucleotides, PC12 cells, mRNA binding
- MeSH terms
- ELAV-Like Protein 4, Animals, Base Sequence, Cell Differentiation, Humans, Microtubules, Molecular Sequence Data, Molecular Weight, Nerve Tissue Proteins, Neurons, RNA, Messenger, Oligonucleotides, Antisense, Neurites, RNA-Binding Proteins, PC12 Cells, Cell Polarity, tau Proteins, Reverse Transcriptase Polymerase Chain Reaction, Caenorhabditis elegans Proteins, Rats, ELAV Proteins
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