3-Hydroxy-3-methylglutaryl coenzyme A synthase-1 of Blattella germanica has structural and functional features of an active retrogene.
Blattella germanica has two cytosolic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase genes, HMG-CoA synthase-1 and -2. HMG-CoA synthase-1 gene shows several features of processed genes (retroposons): it contains no introns but has a short direct-repeat sequence (ATTATTATT) at both ends. An atypical feature is the presence at both ends of the gene of short inverse repeats flanked by direct repeats. There is neither a TATA box nor a CAAT box in the 5' region. Comparative analysis with other species suggests that the HMG-CoA synthase-1 gene derives from HMG-CoA synthase-2. Cultured embryonic B. germanica UM-BGE-1 cells express HMG-CoA synthase-1 but not HMG-CoA synthase-2, suggesting that the intron-less gene is functional. In addition, it can complement MEV-1 cell line, which is auxotrophic for mevalonate. We show that compactin and mevalonate do not significantly affect the mRNA levels of HMG-CoA synthase-1 in UM-BGE-1 cells. Compactin induces a 6.7-fold increase in HMG-CoA reductase activity, which is restored to normal levels by mevalonate. HMG-CoA synthase activity is not modified by either of these effectors, suggesting that the mevalonate pathway in this insect cell line is regulated by post-transcriptional mechanisms affecting HMG-CoA reductase but not HMG-CoA synthase.
Casals
N
N
Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E-08028, Barcelona, Spain. ncasals@csc.unica.edu
Buesa
C
C
Marrero
P F
PF
Belles
X
X
Hegardt
F G
FG
D000818:Animals; D001483:Base Sequence; D003058:Cockroaches / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D017344:Genes, Insect; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000096:biosynthesis / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics*; D007438:Introns; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism; D008969:Molecular Sequence Data; D018626:Retroelements; D013045:Species Specificity
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019476:Insect Proteins; D018626:Retroelements; C012258:mevastatin; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D006904:Hydroxymethylglutaryl-CoA Synthase; D008798:Mevalonic Acid