Molecular cloning, expression and physical mapping of the human methioninesynthase reductase gene

Methionine synthase reductase (EC 2.1.1.135) is a flavoprotein essential fo r maintenance of methionine synthase in an active state. We characterized t he human gene for methionine synthase reductase (MTRR). The gene is approxi mately 34 kb and comprises 15 exons, varying in size from 43 to 1213 bp, an d 14 introns whose sizes vary from 108 bp to 5 kb. The positions of several junctions are conserved between the MTRR gene and the C. elegans ortholog, as well as with the rat cytochrome P450 reductase gene. A 1.3 kb CpG islan d encompasses the 5'-flanking region and exon 1 and extends into intron 1. A short region including the transcription start site is sufficient to conf er promoter activity, with a better outcome when accompanied by intron 1. T he promoter region contains putative binding sites for Spl, AP-1, AP-2 as w ell as CAAT motifs, but no consensus TATA box. Primer extension analysis re vealed a single major transcription start site, located 137 bp upstream of the previously reported initiator ATG. An alternative splicing event involv ing a portion of exon 1 predicts that translation can potentially be initia ted at two different ATG codons. The gene was physically assigned to a narr ow area between markers WI1755 and D5S1957. (C) 1999 Elsevier Science B.V. All rights reserved.