Nyikó Tünde, Auber Andor, Szabadkai Levente, Benkovics Anna, Auth Mariann, Mérai Zsuzsanna, Kerényi Zoltán, Dinnyés Andrea, Nagy Ferenc, Silhavy Dániel
Department of Genetics, Agricultural Biotechnology Institute, Gödöllo, Szent-Györgyi 4, H-2100, Hungary.
Institute of Plant Biology, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Temesvári 62, H-6726, Hungary.
Nucleic Acids Res. 2017 Apr 20;45(7):4174-4188. doi: 10.1093/nar/gkw1303.
When a ribosome reaches a stop codon, the eukaryotic Release Factor 1 (eRF1) binds to the A site of the ribosome and terminates translation. In yeasts and plants, both over- and underexpression of eRF1 lead to altered phenotype indicating that eRF1 expression should be strictly controlled. However, regulation of eRF1 level is still poorly understood. Here we show that expression of plant eRF1 is controlled by a complex negative autoregulatory circuit, which is based on the unique features of the 3΄untranslated region (3΄UTR) of the eRF1-1 transcript. The stop codon of the eRF1-1 mRNA is in a translational readthrough promoting context, while its 3΄UTR induces nonsense-mediated decay (NMD), a translation termination coupled mRNA degradation mechanism. We demonstrate that readthrough partially protects the eRF1-1 mRNA from its 3΄UTR induced NMD, and that elevated eRF1 levels inhibit readthrough and stimulate NMD. Thus, high eRF1 level leads to reduced eRF1-1 expression, as weakened readthrough fails to protect the eRF1-1 mRNA from the more intense NMD. This eRF1 autoregulatory circuit might serve to finely balance general translation termination efficiency.
当核糖体到达终止密码子时,真核释放因子1(eRF1)会与核糖体的A位点结合并终止翻译。在酵母和植物中,eRF1的过表达和低表达都会导致表型改变,这表明eRF1的表达应该受到严格控制。然而,目前对eRF1水平的调控仍知之甚少。在这里,我们表明植物eRF1的表达受一个复杂的负向自调控回路控制,该回路基于eRF1-1转录本3′非翻译区(3′UTR)的独特特征。eRF1-1 mRNA的终止密码子处于促进翻译通读的环境中,而其3′UTR会诱导无义介导的衰变(NMD),这是一种与翻译终止偶联的mRNA降解机制。我们证明,通读可部分保护eRF1-1 mRNA免受其3′UTR诱导的NMD影响,并且eRF1水平升高会抑制通读并刺激NMD。因此,高eRF1水平会导致eRF1-1表达降低,因为减弱的通读无法保护eRF1-1 mRNA免受更强的NMD影响。这种eRF1自调控回路可能有助于精细平衡一般的翻译终止效率。