SMG‐5, required for C.elegans nonsense‐mediated mRNA decay, associates with SMG‐2 and protein phosphatase 2A

mRNAs that contain premature stop codons are degraded selectively and rapidly in eukaryotes, a phenomenon termed ‘nonsense‐mediated mRNA decay’ (NMD). We report here molecular analysis of smg‐5 , which encodes a novel protein required for NMD in Caenorhabditis elegans . Using a combination of immunoprecipitation and yeast two‐hybrid assays, we identified a series of protein–protein interactions involving SMG‐5. SMG‐5 interacts with at least four proteins: (i) SMG‐7, a previously identified protein required for NMD; (ii) SMG‐2, a phosphorylated protein required for NMD in worms, yeasts and mammals; (iii) PR65, the structural subunit of protein phosphatase 2A (PP2A); and (iv) PP2A C , the catalytic subunit of PP2A. Previous work demonstrated that both SMG‐5 and SMG‐7 are required for efficient dephosphorylation of SMG‐2. Our results suggest that PP2A is the SMG‐2 phosphatase, and the role of SMG‐5 is to direct PP2A to its SMG‐2 substrate. We discuss cycles of SMG‐2 phosphorylation and their roles in NMD.