硒代半胱氨酸
生物
硒蛋白
转移RNA
终止密码子
生物化学
遗传学
翻译(生物学)
基因
核糖核酸
信使核糖核酸
酶
半胱氨酸
谷胱甘肽
谷胱甘肽过氧化物酶
作者
Ze Liu,Justin Wang,Yi Shi,Brian A. Yee,Markus Terrey,Qian Zhang,Jenq‐Chang Lee,Kuo‐I Lin,Andrew H-J Wang,Susan L. Ackerman,G Yeo,Haissi Cui,Xiang-Lei Yang
摘要
Translational readthrough of UGA stop codons by selenocysteine-specific tRNA (tRNASec) enables the synthesis of selenoproteins. Seryl-tRNA synthetase (SerRS) charges tRNASec with serine, which is modified into selenocysteine and delivered to the ribosome by a designated elongation factor (eEFSec in eukaryotes). Here we found that components of the human selenocysteine incorporation machinery (SerRS, tRNASec, and eEFSec) also increased translational readthrough of non-selenocysteine genes, including VEGFA, to create C-terminally extended isoforms. SerRS recognizes target mRNAs through a stem-loop structure that resembles the variable loop of its cognate tRNAs. This function of SerRS depends on both its enzymatic activity and a vertebrate-specific domain. Through eCLIP-seq, we identified additional SerRS-interacting mRNAs as potential readthrough genes. Moreover, SerRS overexpression was sufficient to reverse premature termination caused by a pathogenic nonsense mutation. Our findings expand the repertoire of selenoprotein biosynthesis machinery and suggest an avenue for therapeutic targeting of nonsense mutations using endogenous factors.
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