CK2를 매개로 하는TEL2의 인산화에 의한 SMG1의 안정성 증가가 nonsense-mediated mRNA decay에 미치는 영향

Abstract

Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism that degrades a premature-termination codon (PTC)-containing mRNA. During mammalian NMD, suppressor with morphological effect on genitalia (SMG) 1 and up-frameshift factor (UPF) 1, key proteins in NMD, join at a PTC and form an SMG1-UPF1-eRF1-eRF3 (SURF) complex by binding UPF1 to heterodimeric eukaryotic translation release factor (eRF) 3 after PTC-recognition by the translating ribosome. Subsequently, UPF1 is phos- phorylated after UPF1-SMG1 moves onto the downstream exon junction complex (EJC). However, the cellular events that induce UPF1 and SMG1 complex formation and increase NMD efficiency before PTC recognition remain unclear. Here, we show that telomere-maintenance (TEL) 2 phosphorylation by casein-kinase (CK) 2 increases SMG1 stability, which increases UPF1 phosphorylation and, ultimately, augments NMD. Inhibition of CK2 activity or downregulation of TEL2 impairs NMD. Intriguingly, loss of TEL2 phosphorylation reduces UPF1-bound PTC-containing mRNA and the formation of the SMG1-UPF1 complex. Thus, our results identify a new function of CK2-mediated TEL2 phosphorylation in a mammalian NMD.