Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7

Mol Cell. 2003 Nov;12(5):1187-200. doi: 10.1016/s1097-2765(03)00443-x.


Eukaryotic mRNAs containing premature termination codons (PTCs) are degraded by a process known as nonsense-mediated mRNA decay (NMD). NMD has been suggested to require the recognition of PTC by an mRNA surveillance complex containing UPF1/SMG-2. In multicellular organisms, UPF1/SMG-2 is a phosphoprotein, and its phosphorylation contributes to NMD. Here we show that phosphorylated hUPF1, the human ortholog of UPF1/SMG-2, forms a complex with human orthologs of the C. elegans NMD proteins SMG-5 and SMG-7. The complex also associates with protein phosphatase 2A (PP2A), resulting in dephosphorylation of hUPF1. Overexpression of hSMG-5 mutants that retain interaction with P-hUPF1 but which cannot induce its dephosphorylation impair NMD, suggesting that NMD requires P-hUPF1 dephosphorylation. We also show that P-hUPF1 forms distinct complexes containing different isoforms of hUPF3A. We propose that sequential phosphorylation and dephosphorylation of hUPF1 by hSMG-1 and PP2A, respectively, contribute to the remodeling of the mRNA surveillance complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Fractionation
  • Codon, Nonsense
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Phosphatase 2
  • RNA Helicases
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Sequence Alignment
  • Trans-Activators*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Codon, Nonsense
  • Macromolecular Substances
  • RNA, Messenger
  • SMG-5 protein, C elegans
  • SMG-7 protein, C elegans
  • Trans-Activators
  • Transcription Factors
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • RNA Helicases
  • UPF1 protein, human

Associated data

  • GENBANK/AB018275
  • GENBANK/AB085674
  • GENBANK/AB085691