Department of Biochemistry and Molecular Pharmacology, Institute for Systems Genetics, NYU Langone Health, New York, United States
Hua Jiang
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States
Emily M Adney
Department of Biochemistry and Molecular Pharmacology, Institute for Systems Genetics, NYU Langone Health, New York, United States; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States
Aleksandra Wudzinska
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States
Sana Badri
Department of Pathology, NYU Langone Health, New York, United States
Dmitry Ischenko
Moscow Institute of Physics and Technology, Dolgoprudny, Russia
George Eng
Department of Pathology, Massachusetts General Hospital, Boston, United States
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States
Department of Biochemistry and Molecular Pharmacology, Institute for Systems Genetics, NYU Langone Health, New York, United States; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States
Long Interspersed Nuclear Element-1 (LINE-1, L1) is a mobile genetic element active in human genomes. L1-encoded ORF1 and ORF2 proteins bind L1 RNAs, forming ribonucleoproteins (RNPs). These RNPs interact with diverse host proteins, some repressive and others required for the L1 lifecycle. Using differential affinity purifications, quantitative mass spectrometry, and next generation RNA sequencing, we have characterized the proteins and nucleic acids associated with distinctive, enzymatically active L1 macromolecular complexes. Among them, we describe a cytoplasmic intermediate that we hypothesize to be the canonical ORF1p/ORF2p/L1-RNA-containing RNP, and we describe a nuclear population containing ORF2p, but lacking ORF1p, which likely contains host factors participating in target-primed reverse transcription.