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

doi:10.7554/eLife.30058

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 journal › Article

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 language	English (US)
Article number	e30058
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.30058
State	Published - Jan 8 2018

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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title = "LINE-1 protein localization and functional dynamics during the cell cycle",

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{\textquoteleft}s lifecycle and the processes involved in restricting its insertion and intragenomic spread remains elusive. Here we identify modes of L1 proteins{\textquoteright} 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.",

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AU - Mita, Paolo

AU - Wudzinska, Aleksandra

AU - Sun, Xiaoji

AU - Andrade, Joshua

AU - Nayak, Shruti

AU - Kahler, David J.

AU - Badri, Sana

AU - LaCava, John

AU - Ueberheide, Beatrix

AU - Yun, Chi Y.

AU - Fenyö, David

AU - Boeke, Jef D.

PY - 2018/1/8

Y1 - 2018/1/8

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