HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells
Abstract
HuD is one of a family of neural antigens recognised by the sera of patients with antibody-associated paraneoplastic encephalomyelitis. Localised exclusively to neurons, these proteins are among the earliest markers of the developing nervous system. Sequence analysis suggests that HuD is an RNA-binding protein. Hu protein levels were determined for the three cell types characterising human neuroblastoma cell lines: sympathoadrenal neuroblasts (N), substrate-adherent Schwann/glial/melanoblastic precursors (S) and stem cells (I) which can give rise to both N and S cells. Western blot analysis showed similar levels of protein in three N-type cell lines; S cells have no detectable Hu protein. Northern blot analysis indicated that N cells express all three Hu genes, HuD, HuC and Hel-N1. N cells, mostly from MYCN-amplified cell lines, have consistently higher steady-state levels of MYCN mRNA than S cell counterparts. Nuclear run-on and mRNA half-life experiments revealed no differences in transcription rate or mRNA stability between N and S cells from the LA-N-1 cell line, implicating differences in post-transcriptional regulation. HuD is postulated to be instrumental in splicing/processing and/or stabilisation of mRNAs involved in cell growth and neuronal differentiation. As determined by gel-mobility shift assays, HuD fusion protein binds to the 3'UTR of human MYCN mRNA. Analysis of HuD deletion mutants has demonstrated that the first and second RNA-recognition motifs (RRMs) are…
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The first two RRMs of HuD bind to cis-acting elements, typically in the 3′ UTR, while the third RRM interacts with the poly(A) tail of transcripts and stabilizes the RBP-mRNA complex.
“Deletion and mutational analysis of the HuD protein revealed that the first two RRMs bind to the cis-acting elements, typically in the 3′ UTR, while the third RRM interacts with the poly(A) tail of transcripts and stabilizes the RBP-mRNA complex (Chung et al. 1996, 1997; Ma et al. 1997; Ross et al. 1997; Anderson et al. 2000; Park et al. 2000; Wang and Tanaka Hall 2001; Beckel-Mitchener et al. 200”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Ross et al. 1997
HuD binds short-lived mRNAs whose protein product functions in cell proliferation, such as N-myc and c-myc.
“Numerous other ARE-harboring transcripts, such as N-myc and c-myc, were later identified as targets of HuD using similar in vitro approaches, indicating that HuD binds short-lived mRNAs whose protein product functions in cell proliferation (Liu et al. 1995; Ross et al. 1997).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Ross et al. 1997
Cites
Paraneoplastic Encephalomyelitis Antigens Bind to the AU-rich Elements of mRNA
Liu, J., Dalmau, J., Szabo, A., Rosenfeld, M., Huber, J., & Furneaux, H. (1995) · Neurology · doi:10.1212/wnl.45.3.544 · Cited by 122 · see citing works
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The RNA-binding protein HuD regulates neuronal cell identity and maturation
Akamatsu, W., Fujihara, H., Mitsuhashi, T., Yano, M., Shibata, S., Hayakawa, Y., Okano, H. J., Sakakibara, S.-I., Takano, H., Takano, T., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407523102 · Cited by 222 · see citing works
Defining a neuron: neuronal ELAV proteins
Pascale, A., Amadio, M., & Quattrone, A. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7017-y · Cited by 158 · see citing works
Bronicki, L. M., & Jasmin, B. J. (2013) · RNA · doi:10.1261/rna.039164.113 · Cited by 126 · see citing works
RNA–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
- Authors
- Ross, R. A., Lazarova, D. L., Manley, G. T., Smitt, P. S., Spengler, B. A., Posner, J. B., & Biedler, J. L.
- Affiliations
- Fordham University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Ross, R.A
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 33
- Issue
- 12
- Pages
- 2071-2074
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2009087469
- Cited by
- 34
- References
- 1
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca041520-07)
- National Cancer Institute (CA-41520)
- National Institute of Neurological Disorders and Stroke (NS 2604)
- Topics
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- HUD, RNA-binding proteins, MYCN, neuroblastoma, post-transcriptional regulation, 3' untranslated region, RNA recognition motif, mRNA stability, HuC, neuronal differentiation, MYCN amplification, tumor aggressiveness
- MeSH terms
- ELAV-Like Protein 4, Binding Sites, Humans, Neoplasm Proteins, Nerve Tissue Proteins, Neuroblastoma, Protein Binding, RNA, Messenger, Tumor Cells, Cultured, Blotting, Northern, Proto-Oncogene Proteins c-myc, RNA-Binding Proteins, Sequence Deletion, ELAV Proteins
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