RNA Decay Factor UPF1 Promotes Protein Decay: A Hidden Talent

Bioessays. 2018 Jan;40(1):10.1002/bies.201700170. doi: 10.1002/bies.201700170. Epub 2017 Dec 13.


The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay (NMD) pathway. Feng et al. now report a new function for UPF1-it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. UPF1 achieves this through its RING-like domain, which confers ubiquitin E3 ligase activity. Feng et al. provide evidence that the ability of UPF1 to destabilize MYOD represses myogenesis. In the future, it will be important to define other protein substrates of UPF1-driven ubiquitination and to determine whether this biochemical activity is responsible for some of UPF1's previously defined biological functions, including in development and stress responses. The exciting findings presented by Feng et al. open up the possibility that protein turnover and RNA turnover are coupled processes.

Keywords: E3 ligase; development; myogenesis; nonsense-mediated decay; proteasome; ubiquitination.

Publication types

  • Review

MeSH terms

  • Epigenetic Repression
  • Humans
  • Muscle Development
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Nonsense Mediated mRNA Decay*
  • Proteolysis
  • Proteome
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination


  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • Proteome
  • Trans-Activators
  • Ubiquitin-Protein Ligases
  • RNA Helicases
  • UPF1 protein, human