title: The genomic sequence of the murine major vault protein and its promoter.
abstract: Vaults are ribonucleoproteins of unknown function, consisting of three different proteins and multiple copies of small untranslated RNA molecules. One of the protein subunits has been identified as TEP1, a protein that is also associated with the telomerase complex. Another protein appears to contain a functional PARP domain and is hence called VPARP. The third protein, major vault protein (MVP), is believed to make up 70% of the total mass of the vault complex and to be responsible for the typical barrel-shaped structure of vaults. We have isolated the murine MVP cDNA and compared the amino acid sequence with MVP from other species. Over 90% of sequence identity was found between mouse, human and rat, and a considerable degree of identity between mouse and MVPs from lower eukaryotes. We also found that the genomic structure of the murine MVP gene closely resembles the organization of the human MVP gene, both consisting of 15 exons of which most have exactly the same size. Finally we have isolated a genomic region upstream (and partially overlapping) the first untranslated exon, that displayed promoter activity in a luciferase reporter assay. Furthermore, we showed that the sequences from the first exon together with the 5'-end of the first intron enhance the promoter activity, implying the presence of essential promoter elements in this region. Alignment of the murine promoter region with the homologous sequences of the human gene revealed an identity of 58%. The apparent presence of conserved promoter elements suggests a similar regulation of human and murine MVP expression.
authors.affiliation: Department of Hematology, Erasmus University, P.O. Box 1738, 3000 DR, The, Rotterdam, Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Mossink
authors.forename: Arend
authors.initials: A
authors.lastname: van Zon
authors.forename: Erna
authors.initials: E
authors.lastname: Fränzel-Luiten
authors.forename: Martijn
authors.initials: M
authors.lastname: Schoester
authors.forename: George L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Erik A C
authors.initials: EA
authors.lastname: Wiemer
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D005796:Genes / Q000235:genetics; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics*; D000099187:Major Vault Protein
chemical_list: D004247:DNA; D018076:DNA, Complementary; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein