MOLECULAR MECHANISM OF REGULATION OF PENTYLENETETRAZOL-INDUCED CALCIUM-ENTRY BY 3'-UNTRANSLATED REGION OF A SEIZURE-RELATED CDNA, PTZ-17, IN XENOPUS OOCYTES

To determine the molecular mechanism of regulation of pentylenetetrazo l (PTZ)-induced calcium entry by the seizure-related gene, PTZ-17, the role of the 3'-untranslated region (3'UTR) and also interaction betwe en 3'UTR and intracellular factors were investigated. PTZ-induced calc ium inward current in Xenopus oocytes injected with PTZ-17 RNA varied in magnitude among strains of mice: RNA derived from the DBA/2 mouse, which has a high susceptibility to convulsions, showed the largest cur rent and that from the BALB/c mouse with a low susceptibility to convu lsions showed no PTZ response. The sequence of 3'UTR showed alteration s among mouse strains: 3'UTR of BALB/c showed a sequence alteration fr om T to G and that of DBA/2 showed a GTG insertion compared with that of B6. The 3'UTR also regulated the translation of chloramphenicol ace tyltransferase (CAT) RNA depending on its sequence. A particular regio n within the 3'UTR demonstrated interaction with 60- and 47-kDa protei ns. Sequence alterations in this region corresponded to disappearance or increase in PTZ-induced calcium entry. These findings suggest that a particular region within 3'UTR of the seizure-related gene, PTZ-17, is involved in PTZ-induced calcium entry via interaction between mRNA and specific RNA-binding proteins. (C) 1997 Elsevier Science B.V. All rights reserved.