Rebbapragada Indrani, Lykke-Andersen Jens
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Curr Opin Cell Biol. 2009 Jun;21(3):394-402. doi: 10.1016/j.ceb.2009.02.007. Epub 2009 Apr 7.
The nonsense-mediated mRNA decay (NMD) pathway targets mRNAs with premature termination codons as well as a subset of normal mRNAs for rapid decay. Emerging evidence suggests that mRNAs become NMD substrates based on the composition of the mRNP downstream of the translation termination event, which either stimulates or antagonizes recruitment of the NMD machinery. The NMD mRNP subsequently undergoes several remodeling events, which involve hydrolysis of ATP by the NMD factor Upf1 and in metazoans, a phosphorylation/dephosphorylation cycle of Upf1 mediated by Smg proteins. This leads to mRNA decay following translational repression. Recent evidence suggests that in Drosophila and human cells, decay is initiated by the endonuclease Smg6.
无义介导的mRNA降解（NMD）途径将带有提前终止密码子的mRNA以及一部分正常mRNA作为快速降解的靶标。新出现的证据表明，mRNA基于翻译终止事件下游mRNP的组成成为NMD底物，这既刺激也拮抗NMD机制的招募。随后，NMD mRNP经历了几个重塑事件，其中涉及NMD因子Upf1对ATP的水解，在后生动物中，还涉及由Smg蛋白介导的Upf1的磷酸化/去磷酸化循环。这导致翻译抑制后mRNA的降解。最近的证据表明，在果蝇和人类细胞中，降解由核酸内切酶Smg6启动。
