ABSTRACT
N onsense-mediated mRNA decay (NMD) in higher eukaryotes requires the phosphorylation and dephosphorylation of U p fl, an RNA helicase. Recent studies suggest that sequential phosphorylation and dephosphorylation of Upfl follows the recog nition o f premature termination codons within mRNAs and is required for NM D. Upfl phosphorylation, which is mediated by the phosphoinositide 3-kinase-related protein kinase SMG-1, triggers remodeling of the Upfl-containing surveillance complex to form another complex. This second complex, which contains SMG-5, SMG-7 and protein phosphatase 2A, is required for Upfl dephosphorylation. U pfl phosphorylation requires a SMG-1-Upfl complex that interacts directly with the exon junction complex component Upf2, support ing the conclusion that Upfl phosphorylation occurs on mRNA during the mRNA surveil lance process.
