title: Nucleostemin and GNL3L exercise distinct functions in genome protection and ribosome synthesis, respectively.
abstract: The mammalian nucleolar proteins nucleostemin and GNL3-like (GNL3L) are encoded by paralogous genes that arose from an ancestral invertebrate gene, GNL3. Invertebrate GNL3 has been implicated in ribosome biosynthesis, as has its mammalian descendent, GNL3L. The paralogous mammalian nucleostemin protein has, instead, been implicated in cell renewal. Here, we found that depletion of nucleostemin in a human breast carcinoma cell line triggers prompt and significant DNA damage in S-phase cells without perturbing the initial step of ribosomal (r)RNA synthesis and only mildly affects the total ribosome production. By contrast, GNL3L depletion markedly impairs ribosome production without inducing appreciable DNA damage. These results indicate that, during vertebrate evolution, GNL3L retained the role of the ancestral gene in ribosome biosynthesis, whereas the paralogous nucleostemin acquired a novel genome-protective function. Our results provide a coherent explanation for what had seemed to be contradictory findings about the functions of the invertebrate versus vertebrate genes and are suggestive of how the nucleolus was fine-tuned for a role in genome protection and cell-cycle control as the vertebrates evolved.
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Lin
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Meng
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Tsung-Chin
authors.initials: TC
authors.lastname: Lin
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: Program in Cell and Developmental Dynamics, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Thoru
authors.initials: T
authors.lastname: Pederson
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA rtsai@ibt.tamhsc.edu.
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Tsai
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D016196:S Phase / Q000502:physiology
chemical_list: C469949:GNL3 protein, human; C509155:GNL3L protein, human; D009687:Nuclear Proteins; D019204:GTP-Binding Proteins
keywords: Cell cycle; DNA damage; GNL3L; Nucleolus; Nucleostemin; Ribosomal synthesis