Characterization of SMG-9, an essential component of the nonsense-mediated mRNA decay SMG1C complex

Nucleic Acids Res. 2011 Jan;39(1):347-58. doi: 10.1093/nar/gkq749. Epub 2010 Sep 3.

Abstract

SMG-9 is part of a protein kinase complex, SMG1C, which consists of the SMG-1 kinase, SMG-8 and SMG-9. SMG1C mediated phosphorylation of Upf1 triggers nonsense-mediated mRNA decay (NMD), a eukaryotic surveillance pathway that detects and targets for degradation mRNAs harboring premature translation termination codons. Here, we have characterized SMG-9, showing that it comprises an N-terminal 180 residue intrinsically disordered region (IDR) followed by a well-folded C-terminal domain. Both domains are required for SMG-1 binding and the integrity of the SMG1C complex, whereas the C-terminus is sufficient to interact with SMG-8. In addition, we have found that SMG-9 assembles in vivo into SMG-9:SMG-9 and, most likely, SMG-8:SMG-9 complexes that are not constituents of SMG1C. SMG-9 self-association is driven by interactions between the C-terminal domains and surprisingly, some SMG-9 oligomers are completely devoid of SMG-1 and SMG-8. We propose that SMG-9 has biological functions beyond SMG1C, as part of distinct SMG-9-containing complexes. Some of these complexes may function as intermediates potentially regulating SMG1C assembly, tuning the activity of SMG-1 with the NMD machinery. The structural malleability of IDRs could facilitate the transit of SMG-9 through several macromolecular complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon, Nonsense
  • HeLa Cells
  • Humans
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Stability
  • RNA, Messenger / metabolism

Substances

  • Codon, Nonsense
  • Protein Subunits
  • RNA, Messenger
  • Protein-Serine-Threonine Kinases