Role of SMG-1-mediated Upf1 phosphorylation in mammalian nonsense-mediated mRNA decay

Genes Cells. 2013 Mar;18(3):161-75. doi: 10.1111/gtc.12033. Epub 2013 Jan 28.


SMG-1, a member of the PIKK (phosphoinositide 3-kinase-related kinase) family, plays a critical role in the mRNA quality control system known as nonsense-mediated mRNA decay (NMD). NMD protects cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) which encode nonfunctional or potentially harmful truncated proteins. SMG-1 directly phosphorylates Upf1 helicase, another key component of NMD, upon recognition of PTC on postspliced mRNA during the initial round of translation. Phosphorylated-Upf1 recruits the SMG-5/SMG-7 complex to induce ribosome dissociation and decapping-mediated decay. Phospho-Upf1 also recruits the SMG-6 endonuclease which might be involved in endo-cleavage. Upf1 ATPase/helicase activities are likely required for the activation of other mRNA decay enzymes and the mRNA-protein complex dissociation to complete NMD. At present, a variety of tools are available that can specifically suppress NMD, and it has become possible to examine the contribution of NMD in a variety of physiological and pathological conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Codon, Nonsense
  • Humans
  • Nonsense Mediated mRNA Decay*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • RNA Helicases / metabolism*
  • RNA, Messenger / metabolism
  • Trans-Activators / metabolism*


  • Codon, Nonsense
  • RNA, Messenger
  • Trans-Activators
  • Phosphatidylinositol 3-Kinases
  • Adenosine Triphosphatases
  • RNA Helicases