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Paraneoplastic Encephalomyelitis Antigens Bind to the AU-rich Elements of mRNA
Abstract
The Hu antigens are composed of a family of neuronal-specific, RNA-binding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drosophila protein required for neuronal development and maintenance. Although the three proteins are very similar in structure, they are differentiated by alternative splicing of their mRNAs. We report here that the Hu antigens bind avidly to the AU-rich element resident in many mRNAs that regulate cell proliferation. This interaction suggests that the Hu antigens promote neuronal differentiation by suppressing the neuroblast cell cycle. Such a mechanism provides a plausible model for the role of the Hu antigens in tumorigenesis, neuronal differentiation, and paraneoplastic neurologic disorders.
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“The HuD protein, like all Hu members, has a molecular weight of ∼40 kDa and contains three RNA recognition motifs (RRMs) with a linker region separating the second and third RRM (Fig. 1C; Good 1995; Liu et al. 1995; Okano and Darnell 1997).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Liu et al. 1995
In the citing paper
“Using REMSAs, the authors showed that HuD binds specifically to an ARE sequence in the c-fos 3′ UTR.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Liu et al. 1995
In the citing paper
“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 Liu et al. 1995
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AU-rich elements and associated factors: are there unifying principles?
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Metadata
- Authors
- Liu, J., Dalmau, J., Szabo, A., Rosenfeld, M., Huber, J., & Furneaux, H.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Venue
- Neurology
- Published
- 1995-03
- Volume
- 45
- Issue
- 3
- Pages
- 544-550
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2045309201
- Cited by
- 122
- References
- 33
- Citations by year
- 2025: 1 · 2022: 2 · 2019: 1 · 2017: 1 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns029682-04)
- National Cancer Institute (CA-09512, T32CA009512)
- National Institute of Neurological Disorders and Stroke (NS29682)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- paraneoplastic encephalomyelitis, AU-rich elements, RNA-binding proteins, HUD, alternative splicing, mRNA stability, cell cycle regulation, neuronal differentiation, neuroblastoma, carcinogenesis
- MeSH terms
- ELAV-Like Protein 4, Amino Acid Sequence, Base Sequence, Encephalomyelitis, Exons, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Paraneoplastic Syndromes, RNA, Messenger, RNA, Neoplasm, RNA-Binding Proteins, Genes, fos, ELAV Proteins
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