Journal of Biochemistry Advance Access originally published online on February 27, 2009
Journal of Biochemistry 2009 145(6):733-738; doi:10.1093/jb/mvp030
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Post-Transcriptional Regulation of the Expression of Ferrochelatase by Its Variant mRNA
1Department of Biotechnology and 2Insect Biomedical Center, Kyoto Institute of Technology, Kyoto 606-8585, Japan
*To whom correspondence should be addressed. Tel: +81-75-724-7789, Fax: 81-724-7760, E-mail: taketani{at}kit.ac.jp
Received January 27, 2009; Accepted February 17, 2009
| Abstract |
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Ferrochelatase (FECH) catalyses the insertion of ferrous ions into protoporphyrin IX to produce haem at the haem-biosynthetic pathway. The present study characterized a variant mRNA of mouse FECH, which was generated by skipping exon II (FECH-v). FECH-v mRNA was expressed in various tissues, including the liver and kidney, of mice. The mRNA was also expressed in mouse and human non-erythroid and erythroid cells to a different extent but could not be translated into functional FECH. The ratio of FECH-v/FECH increased in hemin-treated Balb/3T3 cells, while it decreased after treatment with succinylacetone, an inhibitor of haem biosynthesis, strongly suggesting that FECH expression was decreased by increasing the level of intracellular haem. These results demonstrated the haem-dependent negative feedback regulation of the expression of FECH at a post-transcriptional level.
Key Words: ferrochelatase, haem biosynthesis, hemin, mRNA variant, post-transcription
Abbreviations: bp, base pair(s); DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethylsulfoxide; EPP, erythropoietic protoporphyria; FCS, fetal calf serum; FECH, ferrochelatase; FECH-v, ferrochelatase variant; kDa, kilodalton (s); MEL, mouse erythroleukemia; RT–PCR, reverse transcription-polymerase chain reaction; SDS, sodium dodecylsulfate; SA, succinylacetone