title: Mapping the LINE1 ORF1 protein interactome reveals associated inhibitors of human retrotransposition.
abstract: LINE1s occupy 17% of the human genome and are its only active autonomous mobile DNA. L1s are also responsible for genomic insertion of processed pseudogenes and >1 million non-autonomous retrotransposons (Alus and SVAs). These elements have significant effects on gene organization and expression. Despite the importance of retrotransposons for genome evolution, much about their biology remains unknown, including cellular factors involved in the complex processes of retrotransposition and forming and transporting L1 ribonucleoprotein particles. By co-immunoprecipitation of tagged L1 constructs and mass spectrometry, we identified proteins associated with the L1 ORF1 protein and its ribonucleoprotein. These include RNA transport proteins, gene expression regulators, post-translational modifiers, helicases and splicing factors. Many cellular proteins co-localize with L1 ORF1 protein in cytoplasmic granules. We also assayed the effects of these proteins on cell culture retrotransposition and found strong inhibiting proteins, including some that control HIV and other retroviruses. These data suggest candidate cofactors that interact with the L1 to modulate its activity and increase our understanding of the means by which the cell coexists with these genomic 'parasites'.
authors.affiliation: McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine.
authors.forename: John L
authors.initials: JL
authors.lastname: Goodier
authors.forename: Ling E
authors.initials: LE
authors.lastname: Cheung
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D015497:HIV-1; D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011544:Pseudogenes; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D034443:RNA Transport; D018626:Retroelements; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C562346:L1TD1 protein, human; D046912:Multiprotein Complexes; C531245:ORF1 protein, human; D011506:Proteins; D018626:Retroelements; D012261:Ribonucleoproteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C530476:Mov10 protein, human; D020365:RNA Helicases