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SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age

Author

Listed:
  • Michael Van Meter

    (University of Rochester)

  • Mehr Kashyap

    (University of Rochester)

  • Sarallah Rezazadeh

    (University of Rochester)

  • Anthony J. Geneva

    (University of Rochester)

  • Timothy D. Morello

    (University of Rochester)

  • Andrei Seluanov

    (University of Rochester)

  • Vera Gorbunova

    (University of Rochester)

Abstract

L1 retrotransposons are an abundant class of transposable elements that pose a threat to genome stability and may have a role in age-related pathologies such as cancer. Recent evidence indicates that L1s become more active in somatic tissues during the course of ageing; however the mechanisms underlying this phenomenon remain unknown. Here we report that the longevity regulating protein, SIRT6, is a powerful repressor of L1 activity. Specifically, SIRT6 binds to the 5′-UTR of L1 loci, where it mono-ADP ribosylates the nuclear corepressor protein, KAP1, and facilitates KAP1 interaction with the heterochromatin factor, HP1α, thereby contributing to the packaging of L1 elements into transcriptionally repressive heterochromatin. During the course of ageing, and also in response to DNA damage, however, we find that SIRT6 is depleted from L1 loci, allowing the activation of these previously silenced retroelements.

Suggested Citation

  • Michael Van Meter & Mehr Kashyap & Sarallah Rezazadeh & Anthony J. Geneva & Timothy D. Morello & Andrei Seluanov & Vera Gorbunova, 2014. "SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6011
    DOI: 10.1038/ncomms6011
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    Cited by:

    1. Ádám Sturm & Éva Saskői & Bernadette Hotzi & Anna Tarnóci & János Barna & Ferenc Bodnár & Himani Sharma & Tibor Kovács & Eszter Ari & Nóra Weinhardt & Csaba Kerepesi & András Perczel & Zoltán Ivics & , 2023. "Downregulation of transposable elements extends lifespan in Caenorhabditis elegans," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Zhengyi Zhen & Yu Chen & Haiyan Wang & Huanyin Tang & Haiping Zhang & Haipeng Liu & Ying Jiang & Zhiyong Mao, 2023. "Nuclear cGAS restricts L1 retrotransposition by promoting TRIM41-mediated ORF2p ubiquitination and degradation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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