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 pentylenetetrazol (PTZ)-induced calcium entry by the seizure-related gene, PTZ-17, the role of the 3'-untranslated region (3'UTR) and also interaction between 3'UTR and intracellular factors were investigated. PTZ-induced calcium 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 current and that from the BALB/c mouse with a low susceptibility to convulsions showed no PTZ response. The sequence of 3'UTR showed alterations among mouse strains: 3'UTR of BALB/c showed a sequence alteration from 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 acetyltransferase (CAT) RNA depending on its sequence. A particular region within the 3'UTR demonstrated interaction with 60- and 47-kDa proteins. 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.
Kajiwara
K
K
Department of Molecular and Developmental Science, Molecular Medicine Research Center, Tokai University, Isehara, Kanagawa, Japan.
Sugaya
E
E
Yuyama
N
N
Nagasawa
H
H
Tsuda
T
T
Sugaya
A
A
Motoki
M
M
Shimizu-Nishikawa
K
K
Kimura
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D018076:DNA, Complementary / Q000187:drug effects*; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000494:pharmacology*; D012313:RNA / Q000378:metabolism; D012640:Seizures / Q000235:genetics*; D014981:Xenopus
D018076:DNA, Complementary; D012313:RNA; D002118:Calcium; D010433:Pentylenetetrazole