Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense-mediated mRNA decay.

ABSTRACT: Many gene expression factors contain repetitive phosphorylation sites for single kinases, but the functional significance is poorly understood. Here we present evidence for hyperphosphorylation as a mechanism allowing UPF1, the central factor in nonsense-mediated decay (NMD), to increasingly attract downstream machinery with time of residence on target mRNAs. Indeed, slowing NMD by inhibiting late-acting factors triggers UPF1 hyperphosphorylation, which in turn enhances affinity for factors linking UPF1 to decay machinery. Mutational analyses reveal multiple phosphorylation sites contributing to different extents to UPF1 activity with no single site being essential. Moreover, the ability of UPF1 to undergo hyperphosphorylation becomes increasingly important for NMD when downstream factors

SUBMITTER: Durand S 

PROVIDER: S-EPMC4987530 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature