J. Biochem, 1993, Vol. 113, No. 3 364-371
© 1993 Japanese Biochemical Society
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Structure and Expression of the Gene Encoding Rat Nonspecific Form -Aminolevulinate Synthase1
*Biochemistry
**Applied Physiology and Molecular Biology, Tohoku University School of Medicine. 2-1 Seiryomachi, Aoba-ku, Sendai 980
2To whom correspondence should be addressed.
To understand the regulatory mechanisms controlling the heme biosynthetic pathway in animal liver, RNA blot hybridization analysis was used to examine the developmental stage-specific transcription of the gene encoding nonspecific form tf-aminolevulinate synthase (ALAS-N). The expression of the erythroid-specific 5-aminolevulinate synthase (ALAS-E) mRNA was also studied. The results demonstrated that, while ALAS-E is the key enzyme which supplies large quantities of heme for hemoglobin synthesis in fetal rat liver, ALAS-N functions to supply heme for the cytochrome P-460 system in fetal, newborn, and adult rat liver. ALAS-N was also suggested to work as a housekeeper gene to supply heme for respiratory cytochromes and other hemoproteins in various tissues. The structure and organization of the rat ALAS-N gene were next analyzed to study the molecular mechanisms regulating ALAS-N gene transcription. The ALAS-N gene was found to span more than 14 kb in the rat genome, encompassing eleven exons. The promoter region of the gene was found to contain several potential cis-acting regulatory elements, including motifs matching the TATA box sequence and the nuclear respiratory factor 1 binding sequence. The organization of the rat ALAS-N gene was determined to be quite similar to that of the ALAS-E gene in mouse; the mouse ALAS-E gene consists of eleven exons. This observation suggested that the ancestral gene for ALA synthase in animals was probably composed of eleven exons, and both the ALAS-N and ALAS-E genes were derived from this ancestral gene.
1This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture (to NH and MY) and a grant from the Uehara Memorial Foundation (to MY).
3 Present address: Department of Public Health, Toyama Medical and Pharmaceutical University School of Medicine 2630 Sugitani, Toyama, Toyama 930-01.
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