Imamachi N, Tani H, Akimitsu N
Radioisotope Center, The University of Tokyo, Tokyo, Japan.
Drug Discov Ther. 2012 Apr;6(2):55-61.
Up-frameshift protein 1 (UPF1) is an evolutionarily conserved protein with RNA/DNA-dependent ATPase and RNA helicase activity. The protein is well known for its central role in nonsense-mediated mRNA decay (NMD), which eliminates aberrant mRNAs harboring premature termination codon (PTC), preventing the accumulation of nonfunctional or potentially harmful truncated proteins. NMD is also involved in the regulation of the state-levels of many normal physiological mRNAs. Moreover UPF1 is not only a key player in NMD but is also involved in non-NMD RNA degradation, such as staufen1 (STAU1)-mediated mRNA decay (SMD) and replication-dependent histone mRNA decay. Thus, UPF1 is an important factor for the RNA quality control system and the regulation of physiological gene expression. Further, recent studies have clarified that UPF1 contributes to DNA replication, DNA repair, telomere metabolism, and stabilization of HIV-1 genomic RNA. In the review, we summarize numerous functions of UPF1.
移码上游蛋白1(UPF1)是一种具有RNA/DNA依赖性ATP酶和RNA解旋酶活性的进化保守蛋白。该蛋白因其在无义介导的mRNA衰变(NMD)中的核心作用而广为人知,NMD可消除含有提前终止密码子(PTC)的异常mRNA,防止无功能或潜在有害的截短蛋白积累。NMD还参与许多正常生理mRNA的水平调节。此外,UPF1不仅是NMD中的关键因子,还参与非NMD RNA降解,如Staufen1(STAU1)介导的mRNA衰变(SMD)和复制依赖性组蛋白mRNA衰变。因此UPF1是RNA质量控制系统和生理基因表达调控的重要因子。此外,最近的研究表明UPF1有助于DNA复制、DNA修复、端粒代谢以及HIV-1基因组RNA的稳定。在这篇综述中,我们总结了UPF1的众多功能。