无意义介导的衰变
环己酰亚胺
生物
信使核糖核酸
真核翻译
移码突变
翻译(生物学)
蛋白质生物合成
天然产物
细胞生物学
胡说
机制(生物学)
磷酸化
遗传学
外显子
基因
核糖核酸
生物化学
RNA剪接
物理
量子力学
作者
Yongjun Dang,Woon Kai Low,Jin Xu,Niels H. Gehring,Harry C. Dietz,Daniel Romo,Jun O. Liu
标识
DOI:10.1074/jbc.m109.009985
摘要
Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A (PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulate NMD. Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.
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