The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay.
The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay.
复制标题
拮抗基因旁系同源物UPF3A和UPF3B控制了废话介导的RNA衰变。
DOI：
10.1016/j.cell.2016.02.046
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发表时间：
2016-04-07
期刊：
影响因子：
64.5
通讯作者：
Wilkinson MF
中科院分区：
文献类型：
--
作者：
Shum EY;Jones SH;Shao A;Chousal JN;Krause MD;Chan WK;Lou CH;Espinoza JL;Song HW;Phan MH;Ramaiah M;Huang L;McCarrey JR;Peterson KJ;De Rooij DG;Cook-Andersen H;Wilkinson MF
基因复制是推动适应和物种形成的主要进化力量，因为它允许获得新功能，并可以增强或多样化现有功能。在这里，我们报告了一个基因复制事件，产生了另一个结果-拮抗功能的产生。这种复制事件的一种产物-UPF 3B-对于无义介导的RNA衰变（NMD）途径至关重要，而其常染色体对应物-UPF 3A-编码一种先前显示具有痕量NMD活性的神秘蛋白。使用体外和体内功能丧失的方法，我们发现UPF 3A主要作为一种有效的NMD抑制剂，稳定了数百种转录物。有证据表明，UPF 3A通过简单的关键结构域损伤获得阻遏物活性，这是一种可能在进化中广泛使用的快速机制。条件性缺乏UPF 3A的小鼠表现出“超”NMD，并显示胚胎发生和配子发生的缺陷，这与UPF 3A作为指导发育事件的分子变阻器一致。
Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome – the generation of antagonistic functions. One product of this duplication event – UPF3B – is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart – UPF3A – encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit “hyper” NMD and display defects in embryogenesis and gametogenesis, consistent with UPF3A serving as a molecular rheostat that directs developmental events.