LOCUS       NM_028404               1905 bp    mRNA    linear   ROD 06-JUN-2024
DEFINITION  Mus musculus DNA topoisomerase 1, mitochondrial (Top1mt),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_028404 XM_128145
VERSION     NM_028404.3
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (bases 1 to 1905)
  AUTHORS   Al Khatib,I., Deng,J., Lei,Y., Torres-Odio,S., Rojas,G.R.,
            Newman,L.E., Chung,B.K., Symes,A., Zhang,H., Huang,S.N.,
            Pommier,Y., Khan,A., Shadel,G.S., West,A.P., Gibson,W.T. and
            Shutt,T.E.
  TITLE     Activation of the cGAS-STING innate immune response in cells with
            deficient mitochondrial topoisomerase TOP1MT
  JOURNAL   Hum Mol Genet 32 (15), 2422-2440 (2023)
   PUBMED   37129502
  REMARK    GeneRIF: Activation of the cGAS-STING innate immune response in
            cells with deficient mitochondrial topoisomerase TOP1MT.
REFERENCE   2  (bases 1 to 1905)
  AUTHORS   Baechler,S.A., Factor,V.M., Dalla Rosa,I., Ravji,A., Becker,D.,
            Khiati,S., Miller Jenkins,L.M., Lang,M., Sourbier,C.,
            Michaels,S.A., Neckers,L.M., Zhang,H.L., Spinazzola,A., Huang,S.N.,
            Marquardt,J.U. and Pommier,Y.
  TITLE     The mitochondrial type IB topoisomerase drives mitochondrial
            translation and carcinogenesis
  JOURNAL   Nat Commun 10 (1), 83 (2019)
   PUBMED   30622257
  REMARK    GeneRIF: Study demonstrated that lack of TOP1MT results in delayed
            and decreased tumor growth due to impaired mitochondrial
            translation. The TOP1MT genomic signature profile, based on mouse
            model for Top1mt-KO liver cancers, is correlated with enhanced
            survival of hepatocellular carcinoma patients.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1905)
  AUTHORS   Dalla Rosa,I., Zhang,H., Khiati,S., Wu,X. and Pommier,Y.
  TITLE     Transcription profiling suggests that mitochondrial topoisomerase
            IB acts as a topological barrier and regulator of mitochondrial DNA
            transcription
  JOURNAL   J Biol Chem 292 (49), 20162-20172 (2017)
   PUBMED   29021209
  REMARK    GeneRIF: TOP1MT acts as a topological barrier and regulator for
            mtDNA transcription and D-loop formation
REFERENCE   4  (bases 1 to 1905)
  AUTHORS   Khiati,S., Baechler,S.A., Factor,V.M., Zhang,H., Huang,S.Y., Dalla
            Rosa,I., Sourbier,C., Neckers,L., Thorgeirsson,S.S. and Pommier,Y.
  TITLE     Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver
            regeneration
  JOURNAL   Proc Natl Acad Sci U S A 112 (36), 11282-11287 (2015)
   PUBMED   26305952
REFERENCE   5  (bases 1 to 1905)
  AUTHORS   Lefebvre,J., Clarkson,M., Massa,F., Bradford,S.T., Charlet,A.,
            Buske,F., Lacas-Gervais,S., Schulz,H., Gimpel,C., Hata,Y.,
            Schaefer,F. and Schedl,A.
  TITLE     Alternatively spliced isoforms of WT1 control podocyte-specific
            gene expression
  JOURNAL   Kidney Int 88 (2), 321-331 (2015)
   PUBMED   25993318
REFERENCE   6  (bases 1 to 1905)
  AUTHORS   Zhang,H., Zhang,Y.W., Yasukawa,T., Dalla Rosa,I., Khiati,S. and
            Pommier,Y.
  TITLE     Increased negative supercoiling of mtDNA in TOP1mt knockout mice
            and presence of topoisomerases IIalpha and IIbeta in vertebrate
            mitochondria
  JOURNAL   Nucleic Acids Res 42 (11), 7259-7267 (2014)
   PUBMED   24803675
REFERENCE   7  (bases 1 to 1905)
  AUTHORS   Sobek,S., Dalla Rosa,I., Pommier,Y., Bornholz,B., Kalfalah,F.,
            Zhang,H., Wiesner,R.J., von Kleist-Retzow,J.C., Hillebrand,F.,
            Schaal,H., Mielke,C., Christensen,M.O. and Boege,F.
  TITLE     Negative regulation of mitochondrial transcription by mitochondrial
            topoisomerase I
  JOURNAL   Nucleic Acids Res 41 (21), 9848-9857 (2013)
   PUBMED   23982517
REFERENCE   8  (bases 1 to 1905)
  AUTHORS   Douarre,C., Sourbier,C., Dalla Rosa,I., Brata Das,B., Redon,C.E.,
            Zhang,H., Neckers,L. and Pommier,Y.
  TITLE     Mitochondrial topoisomerase I is critical for mitochondrial
            integrity and cellular energy metabolism
  JOURNAL   PLoS One 7 (7), e41094 (2012)
   PUBMED   22911747
REFERENCE   9  (bases 1 to 1905)
  AUTHORS   Zhang,H. and Pommier,Y.
  TITLE     Mitochondrial topoisomerase I sites in the regulatory D-loop region
            of mitochondrial DNA
  JOURNAL   Biochemistry 47 (43), 11196-11203 (2008)
   PUBMED   18826252
REFERENCE   10 (bases 1 to 1905)
  AUTHORS   Zhang,H., Meng,L.H., Zimonjic,D.B., Popescu,N.C. and Pommier,Y.
  TITLE     Thirteen-exon-motif signature for vertebrate nuclear and
            mitochondrial type IB topoisomerases
  JOURNAL   Nucleic Acids Res 32 (7), 2087-2092 (2004)
   PUBMED   15096574
  REMARK    Publication Status: Online-Only
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC116393.10.
            
            On Sep 21, 2017 this sequence version replaced NM_028404.2.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF362952.1, AK147119.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN01164135, SAMN01164139
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-148               AC116393.10        58599-58746         c
            149-261             AC116393.10        55965-56077         c
            262-383             AC116393.10        54238-54359         c
            384-506             AC116393.10        50008-50130         c
            507-694             AC116393.10        49233-49420         c
            695-839             AC116393.10        48572-48716         c
            840-983             AC116393.10        47768-47911         c
            984-1169            AC116393.10        47366-47551         c
            1170-1238           AC116393.10        46199-46267         c
            1239-1353           AC116393.10        45533-45647         c
            1354-1481           AC116393.10        43961-44088         c
            1482-1576           AC116393.10        43302-43396         c
            1577-1723           AC116393.10        37630-37776         c
            1724-1905           AC116393.10        36979-37160         c
FEATURES             Location/Qualifiers
     source          1..1905
                     /organism="Mus musculus"
                     /mol_type="mRNA"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="15"
                     /map="15 34.69 cM"
     gene            1..1905
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /note="DNA topoisomerase 1, mitochondrial"
                     /db_xref="GeneID:72960"
                     /db_xref="MGI:MGI:1920210"
     exon            1..148
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     CDS             45..1826
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /EC_number="5.6.2.1"
                     /note="isoform 1 is encoded by transcript variant 1; DNA
                     topoisomerase I, mitochondrial; mitochondrial
                     topoisomerase I"
                     /codon_start=1
                     /product="DNA topoisomerase I, mitochondrial isoform 1"
                     /protein_id="NP_082680.1"
                     /db_xref="CCDS:CCDS27547.1"
                     /db_xref="GeneID:72960"
                     /db_xref="MGI:MGI:1920210"
                     /translation="MLLLWLRALCRRFQHVPCRVPSCQVSRVAKANRAGWEETSKSSV
                     KWRQLEHKGPYFTPAYEPLPDGVHFLYDGKPLKLSLAAEEVATFYGKMLHLECTSKEV
                     FRRNFFSDWRKEMTPEERRLITHLDKCDFTEIHKHFLERAEARRTLPREQKQKLKEEA
                     EKLQQEFGYCVLDGHREKIGNFKTEPPGLFRGRGDHPKMGMLKRRVMPEDVVINCSRD
                     SKIPEPPAGHQWKEVRSDNTVMWLAAWVEHIQNSFKYVILNPSSKPKGEMDWQKYEVA
                     RRLKGVVDKIRAQYQADWKSPEMKKRQLAVALYFIDKLALRTGNEKEEGETADTVGCC
                     SLRVEHIRLHAPAGGQEHVVELDFLGKDSIRYKNHVTVEKLVFQNLQHFMEDKDPRDD
                     LFDALTTSSLNKHLQDLMEGLTAKVFRTYNASVTLQEQLRVLTRAEDSVTCKVLAYNR
                     ANRAVAVLCNHQRAVPKTFEKSMQTLQKKIETKKAQVAEAQVELQKAETDLRMRGDSK
                     PKSFLQKQRRLLKLEEQLARLCAKATDKEENKQVALGTAKLNYLDPRISIAWCKRFGV
                     PVEKIYNKTQRERFAWAFNQAGEDFEF"
     exon            149..261
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            262..383
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            384..506
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            507..694
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            695..839
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            840..983
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            984..1169
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1170..1238
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1239..1353
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1354..1481
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1482..1576
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1577..1723
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     exon            1724..1905
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1888..1893
                     /regulatory_class="polyA_signal_sequence"
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /note="hexamer: AATAAA"
     polyA_site      1905
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /note="major polyA site"
ORIGIN      
        1 gtggcctcgg aaagcgggca gagcccacgc atgcacgcac acgcatgctg ctgctgtggc
       61 tcagagccct gtgccggcgt ttccagcatg tcccctgccg cgtcccttcc tgtcaggtgt
      121 cccgggtcgc gaaggcgaac agagccgggt gggaagaaac gagcaagagc agtgtgaagt
      181 ggaggcagct ggagcacaag ggcccgtact tcaccccagc ctacgagccc cttcctgacg
      241 gagtgcactt cctctacgat ggcaaaccgc tgaagctgag cttggcagcg gaggaggtcg
      301 ctaccttcta tgggaaaatg ctgcatcttg agtgtacgag caaggaagtc tttcggagga
      361 acttcttcag tgactggcgg aaggagatga cacctgagga gaggaggctc atcacacacc
      421 ttgacaaatg tgacttcacg gagatccata agcacttcct ggaaagagct gaggcccgca
      481 ggaccctgcc cagggagcag aagcagaagc taaaggaaga ggccgagaaa ctgcagcagg
      541 agtttggcta ttgcgtttta gatggccaca gagaaaaaat aggcaatttc aagacggaac
      601 cacccggctt gttccgtggc cgaggtgacc atcccaagat ggggatgttg aagaggaggg
      661 tcatgccaga ggatgtggtc attaactgca gcagggattc caagatccct gagcccccag
      721 ccggtcacca gtggaaagag gtacgctcag ataacacagt catgtggctg gctgcctggg
      781 tggagcacat ccagaactcc ttcaagtatg tcatactgaa ccccagctcc aagccgaagg
      841 gggagatgga ttggcagaag tatgaggtag cgcgacgctt gaagggggtt gtggacaaga
      901 tccgtgccca gtatcaggct gactggaagt caccagaaat gaagaagaga cagctggctg
      961 tcgcccttta ttttattgat aagctggcac tgcggacagg caatgagaag gaagagggcg
     1021 agacggccga caccgtgggc tgctgctcgc tccgtgtgga gcacatccga ctgcacgcgc
     1081 ccgcaggtgg ccaggagcac gttgtagagc tggacttctt gggaaaggat tccatccgct
     1141 ataagaacca cgtgacggtg gagaagctcg tgttccagaa ccttcagcac ttcatggaag
     1201 acaaggaccc tagggatgac ctctttgatg cactgaccac ttccagcctg aacaagcact
     1261 tgcaggactt gatggaaggg ctgacagcca aggtgttccg gacctacaat gcctctgtca
     1321 ctctgcagga gcagctgcgg gtgctgaccc gtgcggaaga cagcgtaacc tgcaaagtct
     1381 tagcttacaa ccgggcgaac cgggctgtgg cagtcctctg taaccatcag agagcagttc
     1441 ccaagacctt cgagaagtcg atgcagacac ttcaaaaaaa gattgagaca aagaaggcac
     1501 aggtggctga ggcacaggta gagctgcaga aagcagagac tgacctgaga atgagagggg
     1561 acagcaaacc caaaagtttc cttcagaagc agcgacgatt gttaaagctg gaagaacagc
     1621 tggcccgatt gtgcgcgaag gccacagaca aggaggagaa taagcaggtg gccctgggca
     1681 ccgccaagct caactatctg gaccccagga tcagcatcgc ctggtgtaag agatttggag
     1741 tgcctgtgga gaagatctac aacaagaccc agagagagag gtttgcctgg gccttcaacc
     1801 aggcaggtga agactttgaa ttctaagcag cctctttgcc gctgaaatgt tctttctcac
     1861 tgtgaagcag tattgtggtt tttctagaat aaaatgtcgg gggaa
//
