【摘要】 无义介导的mRNA降解(nonsense-mediated mRNA decay,NMD)作为真核细胞中重要RNA监控机制,识别并降解开放阅读框中含有提前终止密码子(premature termination codon,PTC)的mRNA,以避免因截短的蛋白产物积累对细胞造成毒害.NMD还调控正常生理基因的表达,暗示其在真核细胞中扮演重要角色.NMD途径的关键是PTC的识别.本文通过3种模型来分别阐述发现于哺乳动物、酵母等不同有机体的识别机制.通常由NMD因子UPF1(up-frameshift)等被招募至含PTC的mRNA上,借助这些因子组装形成"功能复合体"并激活降解.但目前对于PTC识别后的过程仍认识有限,本文通过综述NMD途径的分子机制以更好地理解其生物学意义.更多还原

【Abstract】 Nonsense-mediated mRNA decay(NMD) is a RNA surveillance mechanism that detects the mRNAs harboring premature termination condons(PTC),and triggers the degradation to prevent the accumulation of truncated and potentially harmful proteins.NMD also regulates a subset of wild-type physiological transcripts,indicating that NMD plays an important biological role in eukaryotic cells.The key of NMD pathway is PTC recognition from authentic stop condons during translation.Here we reviewed three models to elucidate different mechanisms found in mammals and invertebrates.The NMD effectors such as UPF1(up-frameshift) are involved in the "functional complex" assembly on PTC containing mRNA,although the details of sequential events remain to be clarified for the variety among different organisms,we present the latest progress in post-PTC recognition events to better understand the molecular mechanism of NMD pathway.更多还原