LINE-1 protein localization and functional dynamics during the cell cycle

Paolo Mita, Aleksandra Wudzinska, Xiaoji Sun, Joshua Andrade, Shruti Nayak, David J. Kahler, Sana Badri, John LaCava, Beatrix Ueberheide, Chi Y. Yun, David Fenyö, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review

Abstract

LINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology. However, a clear understanding of L1‘s lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins’ entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.

Original languageEnglish (US)
Article numbere30058
JournaleLife
Volume7
DOIs
StatePublished - Jan 8 2018

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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