Sheth Ujwal, Parker Roy
Department of Molecular and Cellular Biology, University of Arizona, Tucson, 85721, USA.
Cell. 2006 Jun 16;125(6):1095-109. doi: 10.1016/j.cell.2006.04.037.
In eukaryotes, a specialized pathway of mRNA degradation termed nonsense-mediated decay (NMD) functions in mRNA quality control by recognizing and degrading mRNAs with aberrant termination codons. We demonstrate that NMD in yeast targets premature termination codon (PTC)-containing mRNA to P-bodies. Upf1p is sufficient for targeting mRNAs to P-bodies, whereas Upf2p and Upf3p act, at least in part, downstream of P-body targeting to trigger decapping. The ATPase activity of Upf1p is required for NMD after the targeting of mRNAs to P-bodies. Moreover, Upf1p can target normal mRNAs to P-bodies but not promote their degradation. These observations lead us to propose a new model for NMD wherein two successive steps are used to distinguish normal and aberrant mRNAs.
在真核生物中，一种称为无义介导衰变（NMD）的mRNA降解特殊途径通过识别和降解带有异常终止密码子的mRNA来发挥mRNA质量控制功能。我们证明酵母中的NMD将含有提前终止密码子（PTC）的mRNA靶向到P小体。Upf1p足以将mRNA靶向到P小体，而Upf2p和Upf3p至少部分在P小体靶向的下游起作用以触发脱帽。在mRNA靶向到P小体后，Upf1p的ATP酶活性是NMD所必需的。此外，Upf1p可以将正常mRNA靶向到P小体，但不会促进其降解。这些观察结果使我们提出了一种新的NMD模型，其中使用两个连续步骤来区分正常和异常mRNA。
