Mühlemann Oliver, Eberle Andrea B, Stalder Lukas, Zamudio Orozco Rodolfo
Institute of Cell Biology, University of Berne, Baltzerstrasse 4, CH-3012 Bern, Switzerland.
Biochim Biophys Acta. 2008 Sep;1779(9):538-49. doi: 10.1016/j.bbagrm.2008.06.012. Epub 2008 Jul 8.
Among the different cellular surveillance mechanisms in charge to prevent production of faulty gene products, nonsense-mediated mRNA decay (NMD) represents a translation-dependent posttranscriptional process that selectively recognizes and degrades mRNAs whose open reading frame (ORF) is truncated by a premature translation termination codon (PTC, also called "nonsense codon"). In doing so, NMD protects the cell from accumulating C-terminally truncated proteins with potentially deleterious functions. Transcriptome profiling of NMD-deficient yeast, Drosophila, and human cells revealed that 3-10% of all mRNA levels are regulated (directly or indirectly) by NMD, indicating an important role of NMD in gene regulation that extends beyond quality control [J. Rehwinkel, J. Raes, E. Izaurralde, Nonsense-mediated mRNA decay: Target genes and functional diversification of effectors, Trends Biochem. Sci. 31 (2006) 639-646.[1]]. In this review, we focus on recent results from different model organisms that indicate an evolutionarily conserved mechanism for PTC identification.
在负责防止产生错误基因产物的不同细胞监测机制中，无义介导的mRNA衰变（NMD）是一种依赖翻译的转录后过程，它选择性地识别并降解其开放阅读框（ORF）被提前翻译终止密码子（PTC，也称为“无义密码子”）截断的mRNA。通过这样做，NMD保护细胞免于积累具有潜在有害功能的C末端截短蛋白。对NMD缺陷型酵母、果蝇和人类细胞的转录组分析表明，所有mRNA水平的3-10%受到NMD（直接或间接）调控，这表明NMD在基因调控中的重要作用超出了质量控制范围[J. Rehwinkel, J. Raes, E. Izaurralde, 无义介导的mRNA衰变：靶基因和效应器的功能多样化，《生物化学趋势》31 (2006) 639-646.[1]]。在本综述中，我们关注来自不同模式生物的最新结果，这些结果表明存在一种进化上保守的PTC识别机制。
