title: The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability.
abstract: It was recently discovered that vertebrate genomes contain multiple endogenised nucleotide sequences derived from the non-retroviral RNA bornavirus. Strikingly, some of these elements have been evolutionary maintained as open reading frames in host genomes for over 40 million years, suggesting that some endogenised bornavirus-derived elements (EBL) might encode functional proteins. EBLN1 is one such element established through endogenisation of the bornavirus N gene (BDV N). Here, we functionally characterise human EBLN1 as a novel regulator of genome stability. Cells depleted of human EBLN1 accumulate DNA damage both under non-stressed conditions and following exogenously induced DNA damage. EBLN1-depleted cells also exhibit cell cycle abnormalities and defects in microtubule organisation as well as premature centrosome splitting, which we attribute in part, to improper localisation of the nuclear envelope protein TPR. Our data therefore reveal that human EBLN1 possesses important cellular functions within human cells, and suggest that other EBLs present within vertebrate genomes may also possess important cellular functions.
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Katie N
authors.initials: KN
authors.lastname: Myers
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Barone
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Anil
authors.initials: A
authors.lastname: Ganesh
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Staples
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Howard
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Beveridge
authors.affiliation: Mass Spectrometry Group, The MRC Laboratory of Molecular Biology, Division of Cell Biology, Hills Road, Cambridge, CB2 0QH, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Maslen
authors.affiliation: Mass Spectrometry Group, The MRC Laboratory of Molecular Biology, Division of Cell Biology, Hills Road, Cambridge, CB2 0QH, UK.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Skehel
authors.affiliation: Genome Stability Group, Sheffield Institute for Nucleic Acids (SInFoNiA), Academic Unit of Molecular Oncology, Department of Oncology &Metabolism, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Collis
mesh_terms: D028981:Bornaviridae / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D004249:DNA Damage; D042822:Genomic Instability; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009698:Nucleoproteins / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
chemical_list: D056744:Cyclin B1; C000612894:EBLN1 protein, human; D028861:Nuclear Pore Complex Proteins; D009698:Nucleoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human; C548551:TPRN protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human