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Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination

Author

Listed:
  • Je-Hyun Yoon

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Kotb Abdelmohsen

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Jiyoung Kim

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Xiaoling Yang

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Jennifer L. Martindale

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Kumiko Tominaga-Yamanaka

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Elizabeth J. White

    (University of Maryland School of Medicine)

  • Arturo V. Orjalo

    (Biosearch Technologies, Inc.)

  • John L. Rinn

    (Harvard University)

  • Stefan G. Kreft

    (University of Konstanz)

  • Gerald M. Wilson

    (University of Maryland School of Medicine)

  • Myriam Gorospe

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

Abstract

Although mammalian long non-coding (lnc)RNAs are best known for modulating transcription, their post-transcriptional influence on mRNA splicing, stability and translation is emerging. Here we report a post-translational function for the lncRNA HOTAIR as an inducer of ubiquitin-mediated proteolysis. HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation. HOTAIR levels are highly upregulated in senescent cells, causing rapid decay of targets Ataxin-1 and Snurportin-1, and preventing premature senescence. These results uncover a role for a lncRNA, HOTAIR, as a platform for protein ubiquitination.

Suggested Citation

  • Je-Hyun Yoon & Kotb Abdelmohsen & Jiyoung Kim & Xiaoling Yang & Jennifer L. Martindale & Kumiko Tominaga-Yamanaka & Elizabeth J. White & Arturo V. Orjalo & John L. Rinn & Stefan G. Kreft & Gerald M. W, 2013. "Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3939
    DOI: 10.1038/ncomms3939
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