title: Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.
abstract: Nuclear modifier genes have been proposed to modulate the phenotypic manifestation of human mitochondrial 12S rRNA A1491G mutation associated with deafness in many families world-wide. Here we identified and characterized the putative nuclear modifier gene TRMU encoding a highly conserved mitochondrial protein related to tRNA modification. A 1937bp TRMU cDNA has been isolated and the genomic organization of TRMU has been elucidated. The human TRMU gene containing 11 exons encodes a 421 residue protein with a strong homology to the TRMU-like proteins of bacteria and other homologs. TRMU is ubiquitously expressed in various tissues, but abundantly in tissues with high metabolic rates including heart, liver, kidney, and brain. Immunofluorescence analysis of human 143B cells expressing TRMU-GFP fusion protein demonstrated that the human Trmu localizes and functions in mitochondrion. Furthermore, we show that in families with the deafness-associated 12S rRNA A1491G mutation there is highly suggestive linkage and linkage disequilibrium between microsatellite markers adjacent to TRMU and the presence of deafness. These observations suggest that human TRMU may modulate the phenotypic manifestation of the deafness-associated mitochondrial 12S rRNA mutations.
authors.affiliation: Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Yan
authors.forename: Yelena
authors.initials: Y
authors.lastname: Bykhovskaya
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.forename: Emebet
authors.initials: E
authors.lastname: Mengesha
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Nathan
authors.initials: N
authors.lastname: Fischel-Ghodsian
authors.forename: Min-Xin
authors.initials: MX
authors.lastname: Guan
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D002874:Chromosome Mapping; D003638:Deafness / Q000201:enzymology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D012335:RNA, Ribosomal / Q000235:genetics*; D012359:tRNA Methyltransferases / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D012359:tRNA Methyltransferases; C496706:TRMU protein, human