title: The ancient source of a distinct gene family encoding proteins featuring RING and C(3)H zinc-finger motifs with abundant expression in developing brain and nervous system.
abstract: Intronless genes can arise by germline retrotransposition of a cDNA originating as mRNA from an intron-containing source gene. Previously, we described several members of a family of intronless mammalian genes encoding a novel class of zinc-finger proteins, including one that shows imprinted expression and one that escapes X-inactivation. We report here the identification and characterization of the Makorin ring finger protein 1 gene (MKRN1), a highly transcribed, intron-containing source for this family of genes. Phylogenetic analyses clearly indicate that the MKRN1 gene is the ancestral founder of this gene family. We have identified MKRN1 orthologs from human, mouse, wallaby, chicken, fruitfly, and nematode, underscoring the age and conservation of this gene. The MKRN gene family encodes putative ribonucleoproteins with a distinctive array of zinc-finger motifs, including two to four C(3)H zinc-fingers, an unusual Cys/His arrangement that may represent a novel zinc-finger structure, and a highly conserved RING zinc-finger. To date, we have identified nine MKRN family loci distributed throughout the human genome. The human and mouse MKRN1 loci map to a conserved syntenic group near the T-cell receptor beta cluster (TCRB) in chromosome 7q34-q35 and chromosome 6A, respectively. MKRN1 is widely transcribed in mammals, with high levels in murine embryonic nervous system and adult testis. The ancient origin of MKRN1, high degree of conservation, and expression pattern suggest important developmental and functional roles for this gene and its expressed family members.
authors.affiliation: Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Gray
authors.forename: L
authors.initials: L
authors.lastname: Hernandez
authors.forename: A H
authors.initials: AH
authors.lastname: Carey
authors.forename: M A
authors.initials: MA
authors.lastname: Schaldach
authors.forename: M J
authors.initials: MJ
authors.lastname: Smithwick
authors.forename: K
authors.initials: K
authors.lastname: Rus
authors.forename: J A
authors.initials: JA
authors.lastname: Marshall Graves
authors.forename: C L
authors.initials: CL
authors.lastname: Stewart
authors.forename: R D
authors.initials: RD
authors.lastname: Nicholls
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D003582:Cytogenetics; D018076:DNA, Complementary; D004330:Drosophila; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D005091:Exons; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009419:Nerve Tissue Proteins; D009420:Nervous System / Q000196:embryology* / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D018076:DNA, Complementary; C410808:Makorin ring finger protein 1; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins