SMG7 acts as a molecular link between mRNA surveillance and mRNA decay

Mol Cell. 2004 Nov 19;16(4):587-96. doi: 10.1016/j.molcel.2004.10.013.


Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that eliminates mRNAs containing premature termination codons (PTCs). The proteins UPF1, SMG5, SMG6, and SMG7 are essential NMD factors in metazoa. SMG5 and SMG7 form a complex with UPF1 and interact with each other via their N-terminal domains. Here we show that SMG5 and SMG7 colocalize in cytoplasmic mRNA decay bodies, while SMG6 forms separate cytoplasmic foci. When SMG7 is tethered to a reporter transcript, it elicits its degradation, bypassing the requirement for a PTC, UPF1, SMG5, or SMG6. This activity is mediated by the C-terminal domain of SMG7. In contrast, SMG5 requires SMG7 to trigger mRNA decay and to localize to decay bodies. Our findings indicate that SMG7 provides a link between the NMD and the mRNA degradation machinery by interacting with SMG5 and UPF1 via its N-terminal domain and targeting bound transcripts for decay via its C-terminal domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carbocyanines
  • Carrier Proteins / physiology*
  • Cytoplasm / metabolism
  • Dactinomycin / pharmacology
  • Frameshift Mutation
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Luciferases / metabolism
  • Microscopy, Fluorescence
  • Mutation
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Plasmids
  • Protein Structure, Tertiary
  • RNA Helicases
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Ribonucleoproteins, Small Nuclear / metabolism
  • Templates, Genetic
  • Time Factors
  • Trans-Activators / metabolism
  • Transfection


  • Carbocyanines
  • Carrier Proteins
  • LSM4 protein, human
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Ribonucleoproteins, Small Nuclear
  • SMG7 protein, human
  • Trans-Activators
  • cyanine dye 3
  • Dactinomycin
  • Luciferases
  • RNA Helicases
  • UPF1 protein, human