Paraneoplastic Encephalomyelitis Antigens Bind to the AU-rich Elements of mRNA

Liu, J.; Dalmau, J.; Szabo, A.; Rosenfeld, M.; Huber, J.; Furneaux, H.

doi:10.1212/wnl.45.3.544

Cited by 123Autoimmune Neurological Disorders and TreatmentsRNA Research and SplicingMonoclonal and Polyclonal Antibodies Research

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

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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 has a molecular weight of approximately 40 kDa and contains three RNA recognition motifs (RRMs) with a linker region separating the second and third RRM.
“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
HuD binds specifically to an ARE sequence in the c-fos 3′ UTR.
“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
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 Liu et al. 1995

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Authors: Liu, J., Dalmau, J., Szabo, A., Rosenfeld, M., Huber, J., & Furneaux, H.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
ORCID: Dalmau, J.
Rosenfeld, M.
Furneaux, H.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1995-03
Volume: 45
Issue: 3
Pages: 544-550
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.45.3.544
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 › Neurology › Autoimmune Neurological Disorders and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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Paraneoplastic Encephalomyelitis Antigens Bind to the AU-rich Elements of mRNA

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