LOCUS       NM_018006               1651 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens tRNA mitochondrial 2-thiouridylase (TRMU), transcript
            variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_018006
VERSION     NM_018006.5
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1651)
  AUTHORS   Ahmad,R.N.R., Zhang,L.T., Morita,R., Tani,H., Wu,Y., Chujo,T.,
            Ogawa,A., Harada,R., Shigeta,Y., Tomizawa,K. and Wei,F.Y.
  TITLE     Pathological mutations promote proteolysis of mitochondrial
            tRNA-specific 2-thiouridylase 1 (MTU1) via mitochondrial
            caseinolytic peptidase (CLPP)
  JOURNAL   Nucleic Acids Res 52 (3), 1341-1358 (2024)
   PUBMED   38113276
  REMARK    GeneRIF: Pathological mutations promote proteolysis of
            mitochondrial tRNA-specific 2-thiouridylase 1 (MTU1) via
            mitochondrial caseinolytic peptidase (CLPP).
REFERENCE   2  (bases 1 to 1651)
  AUTHORS   Vogel,G.F., Mozer-Glassberg,Y., Landau,Y.E., Schlieben,L.D.,
            Prokisch,H., Feichtinger,R.G., Mayr,J.A., Brennenstuhl,H.,
            Schroter,J., Pechlaner,A., Alkuraya,F.S., Baker,J.J., Barcia,G.,
            Baric,I., Braverman,N., Burnyte,B., Christodoulou,J., Ciara,E.,
            Coman,D., Das,A.M., Darin,N., Della Marina,A., Distelmaier,F.,
            Eklund,E.A., Ersoy,M., Fang,W., Gaignard,P., Ganetzky,R.D.,
            Gonzales,E., Howard,C., Hughes,J., Konstantopoulou,V., Kose,M.,
            Kerr,M., Khan,A., Lenz,D., McFarland,R., Margolis,M.G.,
            Morrison,K., Muller,T., Murayama,K., Nicastro,E., Pennisi,A.,
            Peters,H., Piekutowska-Abramczuk,D., Rotig,A., Santer,R.,
            Scaglia,F., Schiff,M., Shagrani,M., Sharrard,M., Soler-Alfonso,C.,
            Staufner,C., Storey,I., Stormon,M., Taylor,R.W., Thorburn,D.R.,
            Teles,E.L., Wang,J.S., Weghuber,D. and Wortmann,S.
  TITLE     Genotypic and phenotypic spectrum of infantile liver failure due to
            pathogenic TRMU variants
  JOURNAL   Genet Med 25 (6), 100314 (2023)
   PUBMED   36305855
  REMARK    GeneRIF: Genotypic and phenotypic spectrum of infantile liver
            failure due to pathogenic TRMU variants.
            Erratum:[Genet Med. 2023 Jun;25(6):100828. doi:
            10.1016/j.gim.2023.100828.. PMID: 37272928]
REFERENCE   3  (bases 1 to 1651)
  AUTHORS   Chen,C. and Guan,M.X.
  TITLE     Genetic correction of TRMU allele restored the mitochondrial
            dysfunction-induced deficiencies in iPSCs-derived hair cells of
            hearing-impaired patients
  JOURNAL   Hum Mol Genet 31 (18), 3068-3082 (2022)
   PUBMED   35467742
  REMARK    GeneRIF: Genetic correction of TRMU allele restored the
            mitochondrial dysfunction-induced deficiencies in iPSCs-derived
            hair cells of hearing-impaired patients.
REFERENCE   4  (bases 1 to 1651)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   5  (bases 1 to 1651)
  AUTHORS   Guan,M.X., Yan,Q., Li,X., Bykhovskaya,Y., Gallo-Teran,J., Hajek,P.,
            Umeda,N., Zhao,H., Garrido,G., Mengesha,E., Suzuki,T., del
            Castillo,I., Peters,J.L., Li,R., Qian,Y., Wang,X., Ballana,E.,
            Shohat,M., Lu,J., Estivill,X., Watanabe,K. and Fischel-Ghodsian,N.
  TITLE     Mutation in TRMU related to transfer RNA modification modulates the
            phenotypic expression of the deafness-associated mitochondrial 12S
            ribosomal RNA mutations
  JOURNAL   Am J Hum Genet 79 (2), 291-302 (2006)
   PUBMED   16826519
  REMARK    GeneRIF: The mutated TRMU, related to transfer RNA modification,
            acting as a modifier factor modulates the phenotypic manifestation
            of deafness-associated 12S rRNA mutations.
REFERENCE   6  (bases 1 to 1651)
  AUTHORS   Yan,Q., Bykhovskaya,Y., Li,R., Mengesha,E., Shohat,M., Estivill,X.,
            Fischel-Ghodsian,N. and Guan,M.X.
  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
  JOURNAL   Biochem Biophys Res Commun 342 (4), 1130-1136 (2006)
   PUBMED   16513084
  REMARK    GeneRIF: These observations suggest that human TRMU may modulate
            the phenotypic manifestation of the deafness-associated
            mitochondrial 12S rRNA mutations.
REFERENCE   7  (bases 1 to 1651)
  AUTHORS   Yan,Q., Li,X., Faye,G. and Guan,M.X.
  TITLE     Mutations in MTO2 related to tRNA modification impair mitochondrial
            gene expression and protein synthesis in the presence of a
            paromomycin resistance mutation in mitochondrial 15 S rRNA
  JOURNAL   J Biol Chem 280 (32), 29151-29157 (2005)
   PUBMED   15944150
  REMARK    GeneRIF: MTO2 may act as a modifier gene, modulating the phenotypic
            expression of the deafness-associated A1491G or C1409T mutation in
            mitochondrial 12 S rRNA
REFERENCE   8  (bases 1 to 1651)
  AUTHORS   Umeda,N., Suzuki,T., Yukawa,M., Ohya,Y., Shindo,H., Watanabe,K. and
            Suzuki,T.
  TITLE     Mitochondria-specific RNA-modifying enzymes responsible for the
            biosynthesis of the wobble base in mitochondrial tRNAs.
            Implications for the molecular pathogenesis of human mitochondrial
            diseases
  JOURNAL   J Biol Chem 280 (2), 1613-1624 (2005)
   PUBMED   15509579
  REMARK    GeneRIF: identification and characterization of a tRNA-modifying
            enzyme MTU1 (mitochondrial tRNA-specific 2-thiouridylase 1) that is
            responsible for the 2-thiolation of the wobble position in human
            and yeast mt tRNAs
REFERENCE   9  (bases 1 to 1651)
  AUTHORS   Yan,Q. and Guan,M.X.
  TITLE     Identification and characterization of mouse TRMU gene encoding the
            mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase
  JOURNAL   Biochim Biophys Acta 1676 (2), 119-126 (2004)
   PUBMED   14746906
  REMARK    GeneRIF: Identification and characterization of a mouse gene
            encoding one component of the enzyme complex responsible for the
            nucleotide modification at wobble position of mitochondrial tRNA
            anticodons.
REFERENCE   10 (bases 1 to 1651)
  AUTHORS   Reinhart,M., Muraresku,C. and Ganetzky,R.
  TITLE     TRMU Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   37184193
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AY062123.2 and BC066593.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_018006.4.
            
            Summary: This nuclear gene encodes a mitochondrial tRNA-modifying
            enzyme. The encoded protein catalyzes the 2-thiolation of uridine
            on the wobble positions of tRNA(Lys), tRNA(Glu), and tRNA(Gln),
            resulting in the formation of 5-taurinomethyl-2-thiouridine
            moieties. Mutations in this gene may cause transient infantile
            liver failure. Polymorphisms in this gene may also influence the
            severity of deafness caused by mitochondrial 12S ribosomal RNA
            mutations. Alternative splicing results in multiple transcript
            variants. [provided by RefSeq, Sep 2013].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC066593.1, AY062123.2 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000645190.1/
                                                  ENSP00000496496.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1648              AY062123.2         290-1937
            1649-1651           BC066593.1         1639-1641
FEATURES             Location/Qualifiers
     source          1..1651
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q13.31"
     gene            1..1651
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /note="tRNA mitochondrial 2-thiouridylase"
                     /db_xref="GeneID:55687"
                     /db_xref="HGNC:HGNC:25481"
                     /db_xref="MIM:610230"
     exon            1..133
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     CDS             52..1317
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /EC_number="2.8.1.14"
                     /note="isoform a is encoded by transcript variant 1;
                     mitochondrial
                     5-methylaminomethyl-2-thiouridylate-methyltransferase;
                     mitochondrial tRNA-specific 2-thiouridylase 1; MTO2
                     homolog; lung cancer associated lncRNA 3; tRNA
                     5-methylaminomethyl-2-thiouridylate methyltransferase"
                     /codon_start=1
                     /product="mitochondrial tRNA-specific 2-thiouridylase 1
                     isoform a"
                     /protein_id="NP_060476.2"
                     /db_xref="CCDS:CCDS14075.1"
                     /db_xref="GeneID:55687"
                     /db_xref="HGNC:HGNC:25481"
                     /db_xref="MIM:610230"
                     /translation="MQALRHVVCALSGGVDSAVAALLLRRRGYQVTGVFMKNWDSLDE
                     HGVCTADKDCEDAYRVCQILDIPFHQVSYVKEYWNDVFSDFLNEYEKGRTPNPDIVCN
                     KHIKFSCFFHYAVDNLGADAIATGHYARTSLEDEEVFEQKHVKKPEGLFRNRFEVRNA
                     VKLLQAADSFKDQTFFLSQVSQDALRRTIFPLGGLTKEFVKKIAAENRLHHVLQKKES
                     MGMCFIGKRNFEHFLLQYLQPRPGHFISIEDNKVLGTHKGWFLYTLGQRANIGGLREP
                     WYVVEKDSVKGDVFVAPRTDHPALYRDLLRTSRVHWIAEEPPAALVRDKMMECHFRFR
                     HQMALVPCVLTLNQDGTVWVTAVQAVRALATGQFAVFYKGDECLGSGKILRLGPSAYT
                     LQKGQRRAGMATESPSDSPEDGPGLSPLL"
     exon            134..299
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            300..406
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            407..529
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            530..702
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            703..756
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            757..823
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            824..924
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            925..1069
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1070..1152
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     exon            1153..1651
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1630..1635
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /note="hexamer: AATAAA"
     polyA_site      1651
                     /gene="TRMU"
                     /gene_synonym="LCAL3; MTO2; MTU1; TRMT; TRMT1"
                     /note="major polyA site"
ORIGIN      
        1 aaggcgcgga agcggcggta gctgcagctg gcgaagttgg gcgactggcg gatgcaggcc
       61 ttgcggcacg tcgtgtgcgc cctgtccggc ggcgtggaca gcgccgtggc cgcgctgctg
      121 ctgaggcgga gaggttacca ggtgacaggg gtgtttatga agaactggga ctcactggat
      181 gaacatgggg tctgtactgc cgacaaagac tgtgaagatg cttacagagt ttgccagatc
      241 ttagacatcc ctttccatca agtgtcctac gtaaaggagt attggaatga tgtgttcagt
      301 gactttttga atgagtatga aaaaggaagg actcccaatc ctgacatagt ttgcaacaag
      361 cacatcaaat ttagttgctt ttttcattat gctgtggata atcttggggc agatgccatt
      421 gccacaggtc actatgcaag aacttccctg gaagatgaag aagtctttga gcagaagcac
      481 gttaagaagc ccgaagggct tttcagaaat cggtttgaag ttagaaatgc ggtaaaactc
      541 ctccaggcag ctgacagctt taaagaccag accttctttc tcagccaggt ttcccaggat
      601 gccctgagga gaaccatctt ccctctgggg ggattaacga aagagtttgt aaagaaaatc
      661 gctgctgaga atagacttca tcatgtgctt cagaagaaag agagcatggg catgtgtttc
      721 atcgggaaga ggaattttga acatttcctt cttcagtatc tgcagcctcg acctggtcac
      781 tttatttcca tagaagacaa taaggttctg ggaacacata aaggttggtt cctgtatacc
      841 ttgggccaga gagcaaacat aggtggcctg agagagccct ggtacgtggt ggagaaggac
      901 agcgtcaagg gtgacgtgtt tgtggccccc cggacagacc acccagccct gtacagggac
      961 ctgctgagga ccagccgcgt gcactggatt gcggaggagc ctcccgcagc actggtccgg
     1021 gacaagatga tggagtgcca cttccgattc cgccaccaga tggcactagt gccctgtgtg
     1081 ctgaccctca atcaagatgg caccgtgtgg gtgacagctg tgcaggctgt gcgtgccctt
     1141 gccacaggac agtttgctgt gttctacaag ggggacgagt gcctgggcag cgggaagatc
     1201 ctgcggctgg ggccgtctgc ctacacgctc cagaagggcc agcgcagagc tgggatggcc
     1261 actgagagcc ccagtgacag cccagaagat ggtccaggcc tgagtccctt gctctgacag
     1321 agatggatct gctagaagga acctggagag caggacccat ggctgggcgg ctggtgagca
     1381 gtccaggtgc ccaagggcca gcttgctgct gcccaaagca gaggaagccg ggctggctga
     1441 gggtccgaaa agcctgcagg ggcccggcga gccccaggaa gagcctcagc tccaggctgg
     1501 ggctctggct gctggagcat ctgctggctg gtggggtggc ccgagttccc cttcaccgcc
     1561 cccagggagg gtttcccacc tcagagtaca ccgaggggac ctgcagaggg ggctgtcggg
     1621 acagcgtgga ataaacatta tttcaaggac a
//
