UPF1-LIN28A complex regulates Nonsense-mediated mRNA Decay

Abstract

Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that involves the degradation of a premature-termination codon (PTC)-containing mRNA. In this mechanism, a helicase, UPF1, is a key regulator in NMD. Once UPF1 binds to mRNA, other factors such as UPF2, UPF3 and SMG1 are recruited and UPF1 is phosphorylated. Then, SMG5 and SMG7, or SMG6 are recruited, and start to degrade mRNA. Not only UPF1, but also LIN28A, which is a highly conserved RNA-binding protein expressed in stem cells, is related to RNA stability as a function of posttranscriptional regulation. However, none of the previous studies has investigated the interaction between UPF1 and LIN28A. Here, we demonstrate that LIN28A directly binds to UPF1(419-700). We also show that binding of UPF1 and LIN28A blocks NMD. In addition, our results show that LIN28A prefers to bind unphosphorylated UPF1, as well as that the overexpression of exogenous LIN28A decreases phosphorylated UPF1. Taken together, our results suggest that the UPF1- LIN28A complex acts as a transcriptome regulator.