title: Transposition of a reconstructed Harbinger element in human cells and functional homology with two transposon-derived cellular genes.
abstract: Ancient, inactive copies of transposable elements of the PIF/Harbinger superfamily have been described in vertebrates. We reconstructed components of the Harbinger3_DR transposon in zebrafish, including a transposase and a second, transposon-encoded protein that has a Myb-like trihelix domain. The reconstructed Harbinger transposon shows efficient cut-and-paste transposition in human cells and preferentially inserts into a 15-bp consensus target sequence. The Myb-like protein is required for transposition and physically interacts with the N-terminal region of the transposase via its C-terminal domain. The Myb-like protein enables transposition in part by promoting nuclear import of the transposase, by directly binding to subterminal regions of the transposon, and by recruiting the transposase to the transposon ends. We investigated the functions of two transposon-derived human proteins: HARBI1, a domesticated transposase-derived protein, and NAIF1, which contains a trihelix motif similar to that described in the Myb-like protein. Physical interaction, subcellular localization, and DNA-binding activities of HARBI1 and NAIF1 suggest strong functional homologies between the Harbinger3_DR system and their related, host-encoded counterparts. The Harbinger transposon will serve as a useful experimental system for transposon biology and for investigating the enzymatic functions of domesticated, transposon-derived cellular genes.
authors.affiliation: Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Sinzelle
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kapitonov
authors.forename: Dawid P
authors.initials: DP
authors.lastname: Grzela
authors.forename: Tobias
authors.initials: T
authors.lastname: Jursch
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jurka
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Izsvák
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ivics
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics*; D020029:Base Pairing; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D004251:DNA Transposable Elements / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D011485:Protein Binding; D021381:Protein Transport; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D019895:Transposases / Q000737:chemistry / Q000235:genetics*; D015027:Zebrafish
chemical_list: D051017:Apoptosis Regulatory Proteins; D004251:DNA Transposable Elements; C511414:NAIF1 protein, human; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; C528179:HARBI1 protein, human; D019895:Transposases