Structure and expression of the gene encoding rat nonspecific form delta-aminolevulinate synthase.
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 delta-aminolevulinate synthase (ALAS-N). The expression of the erythroid-specific delta-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-450 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.
Yomogida
K
K
Department of Biochemistry, Tohoku University School of Medicine, Sendai.
Yamamoto
M
M
Yamagami
T
T
Fujita
H
H
Hayashi
N
N
D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000740:Anemia / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D005091:Exons; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005798:Genes, Bacterial; D005865:Gestational Age; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016385:TATA Box; D014158:Transcription, Genetic
D012333:RNA, Messenger; D000624:5-Aminolevulinate Synthetase