BRAIN-SPECIFIC PROTEINS BINDING TO THE 3'-UTR OF THE 5-HT2C RECEPTOR MESSENGER-RNA

The 5-HT2C receptor(2) is a prominent serotonin receptor that is uniqu ely expressed in the central nervous system and has been implicated in a variety of psychiatric diseases. While characterizing the 5-HT3C re ceptor gene, we observed that the mRNA contains a long 3' untranslated region that binds multiple brain proteins. Two proteins, molecular we ights 55 and 58 kDa, were of particular interest because they were det ected only in brain regions known to express the 5-HT2C receptor abund antly, namely, the hippocampus and cortex. These proteins bind with hi gh affinity to the 5-HT2C receptor mRNA at its extreme 3' end (K-d = 1 .8 nM), and binding can be specifically competed by selected regions o f the 3' UTR. Furthermore, binding of the 55 and 58 kDa proteins to th e mRNA is directionally specific and shows preference for an AU-rich l oop containing 6 to 7 nucleotides. These results suggest the possibili ty that these two brain specific proteins may play a role in the post- transcriptional regulation of the 5-HT2C receptor, and that post-trans criptional control of 5-HT2C receptor expression may be an important r egulatory mechanism which has not been previously reported for this se rotonin receptor subtype.