PARANEOPLASTIC ENCEPHALOMYELITIS ANTIGENS BIND TO THE AU-RICH ELEMENTS OF MESSENGER-RNA

The Hu antigens are composed of a family of neuronal-specific, RNA-bin ding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drasophila protein required for neuronal development and maintenance. Although the three proteins are very similar in structure, they are d ifferentiated by alternative splicing of their mRNAs. We report here t hat the Hu antigens bind avidly to the AU-rich element resident in man y mRNAs that regulate cell proliferation. This interaction suggests th at the Hu antigens promote neuronal differentiation by suppressing the neuroblast cell cycle. Such a mechanism provides a plausible model fo r the role of the Hu antigens in tumorigenesis, neuronal differentiati on, and paraneoplastic neurologic disorders.