title: RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals.
abstract: DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3β differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3β proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3β-polyribosome association requires TDRD3, which directly interacts with Top3β and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals.
authors.affiliation: Genome Instability and Chromatin Remodeling Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Muzammil
authors.initials: M
authors.lastname: Ahmad
authors.affiliation: Genome Instability and Chromatin Remodeling Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Genome Instability and Chromatin Remodeling Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Lee
authors.affiliation: RNA Regulation Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.affiliation: Genome Instability and Chromatin Remodeling Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, PeKing University, Beijing 1000871, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, National Institute of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Sige
authors.initials: S
authors.lastname: Zou
authors.affiliation: Institute of Biosciences and Bioresources, National Research Council of Italy, Naples 80131, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ciaramella
authors.affiliation: Institut Jacques Monod, CNRS-Université Paris Diderot-UMR7592, 15 rue Hélène Brion, 75205 Paris Cedex, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Debat
authors.affiliation: Institut Jacques Monod, CNRS-Université Paris Diderot-UMR7592, 15 rue Hélène Brion, 75205 Paris Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Nadal
authors.affiliation: Department of Chemistry & Biochemistry, Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
authors.forename: Fenfei
authors.initials: F
authors.lastname: Leng
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, 212 South Hawthorne Drive, Bloomington, IN 47405, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Cellular Organistic Biology, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Grace Ee-Lu
authors.initials: GE
authors.lastname: Siaw
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, 212 South Hawthorne Drive, Bloomington, IN 47405, USA.
authors.forename: Hengyao
authors.initials: H
authors.lastname: Niu
authors.affiliation: Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.affiliation: RNA Regulation Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Institute of Cellular Organistic Biology, Academia Sinica, Taipei 11529, Taiwan Department of Biochemistry, Duke University Medical Center, Durham, NC 73532, USA.
authors.forename: Tao-Shih
authors.initials: TS
authors.lastname: Hsieh
authors.affiliation: Department of Chemistry & Biochemistry, Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, USA.
authors.forename: Yuk-Ching
authors.initials: YC
authors.lastname: Tse-Dinh
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, PeKing University, Beijing 1000871, China wangw@grc.nia.nih.gov.
authors.forename: Dongyi
authors.initials: D
authors.lastname: Xu
authors.affiliation: Genome Instability and Chromatin Remodeling Section, Lab of Genetics, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA xudongyi@pku.edu.cn.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D020134:Catalytic Domain / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D004278:DNA, Superhelical / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D011132:Polyribosomes / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D004278:DNA, Superhelical; D011506:Proteins; D012333:RNA, Messenger; C532746:Tdrd3 protein, human; D012313:RNA; D004264:DNA Topoisomerases, Type I