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

Nat Commun. 2013:4:2939. doi: 10.1038/ncomms3939.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Argonaute Proteins / metabolism
  • Ataxin-1
  • Ataxins
  • Cellular Senescence / genetics
  • ELAV Proteins / metabolism
  • HeLa Cells
  • Humans
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Cap-Binding Proteins / metabolism
  • RNA Stability
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*


  • AGO2 protein, human
  • ATXN1 protein, human
  • Argonaute Proteins
  • Ataxin-1
  • Ataxins
  • ELAV Proteins
  • HOTAIR long untranslated RNA, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Proteins
  • RNA Cap-Binding Proteins
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • Receptors, Cytoplasmic and Nuclear
  • SNUPN protein, human
  • DZIP3 protein, human
  • Ubiquitin-Protein Ligases