Paraneoplastic encephalomyelitis antigens bind to the AU-rich elements of mRNA.
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.
Liu
J
J
Laboratory of Molecular Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Dalmau
J
J
Szabo
A
A
Rosenfeld
M
M
Huber
J
J
Furneaux
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; D004679:Encephalomyelitis / Q000235:genetics* / Q000276:immunology; D005091:Exons; D016762:Genes, fos; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D010257:Paraneoplastic Syndromes / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis*
D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins