Translational stop codon readthrough generates C-terminally extended protein isoforms. While evidence mounts of readthrough as a global phenomenon, proofs of its functional consequences are scarce. We show that readthrough of the mRNA for the Drosophila POU/Oct transcription factor Drifter occurs at a high rate and in a spatiotemporal manner in vivo, reaching above 50% in the prothoracic gland. Phylogenetic analyses suggested that readthrough of drifter is conserved among Dipterans, with C-terminal extensions harboring intrinsically disordered regions, and amino acids streches implied in transcriptional activation. The C-terminally extended Drifter isoform is required for maintaining normal levels of the growth hormone ecdysone through regulation of its biosynthetic genes, acting in synergy with the transcription factor Molting defective. A 14-bp deletion that abolished readthrough, caused prolonged larval development and delayed metamorphosis. This study provides a striking example of alternative genetic decoding that feeds into the progression from one life cycle stage to another.

中文翻译：

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停止POU转录因子的密码子通读调节类固醇生成和发育过渡

翻译终止密码子通读生成C端扩展的蛋白质同工型。尽管越来越多的证据表明通读是一种全球现象，但其功能后果的证据却很少。我们显示果蝇POU / Oct转录因子漂移的mRNA的通读率很高，并以时空方式在体内发生，在前胸腺中达到50％以上。系统发生学分析表明，在Dipterans中，drift的通透性是保守的，C末端的延伸区具有内在的无序区域，而氨基酸条带则暗示了转录激活。C端延伸的Drifter亚型是通过调节其生物合成基因来维持正常水平的生长激素蜕皮激素所必需的，该基因与转录因子Molting缺陷协同作用。一个14 bp的缺失消除了通读，导致幼虫发育延长和变态延迟。这项研究提供了一个引人注目的例子，说明了从一个生命周期阶段发展到另一个生命周期阶段的替代遗传解码。