Department of Reproductive Medicine, University of California San Diego, La Jolla, CA, 92093-0695, USA.
Bioessays. 2018 Jan;40(1). doi: 10.1002/bies.201700170. Epub 2017 Dec 13.
The RNA-binding protein, UPF1, is best known for its central role in the nonsense-mediated RNA decay (NMD) pathway. Feng et al. now report a new function for UPF1-it is an E3 ubiquitin ligase that specifically promotes the decay of a key pro-muscle transcription factor: MYOD. UPF1 achieves this through its RING-like domain, which confers ubiquitin E3 ligase activity. Feng et al. provide evidence that the ability of UPF1 to destabilize MYOD represses myogenesis. In the future, it will be important to define other protein substrates of UPF1-driven ubiquitination and to determine whether this biochemical activity is responsible for some of UPF1's previously defined biological functions, including in development and stress responses. The exciting findings presented by Feng et al. open up the possibility that protein turnover and RNA turnover are coupled processes.
RNA 结合蛋白 UPF1 最主要的功能是在无义介导的 RNA 降解（NMD）途径中发挥核心作用。Feng 等人现在报道了 UPF1 的一个新功能——它是一种 E3 泛素连接酶，可特异性促进关键的成肌转录因子 MYOD 的降解。UPF1 通过其 RING 样结构域发挥作用，该结构域赋予其泛素 E3 连接酶活性。Feng 等人提供的证据表明，UPF1 使 MYOD 不稳定的能力抑制了肌发生。在未来，确定 UPF1 驱动的泛素化的其他蛋白底物，并确定这种生化活性是否是 UPF1 之前定义的一些生物学功能（包括发育和应激反应）的原因，将非常重要。Feng 等人提出的这一令人兴奋的发现，使蛋白质周转和 RNA 周转可能是耦合的过程。
