Antizyme (AZ) interacts with ornithine decarboxylase, which catalyzes the first step of polyamine biosynthesis and recruits it to the proteasome for degradation. Synthesizing the functional AZ protein requires transition of the reading frame at the termination codon. This programmed +1 ribosomal frameshifting is induced by polyamines, but the molecular mechanism is still unknown. In this study, we explored the mechanism of polyamine-dependent +1 frameshifting using a human cell-free translation system. Unexpectedly, spermidine induced +1 frameshifting in the mutants replacing the termination codon at the shift site with a sense codon. Truncation experiments showed that +1 frameshifting occurred promiscuously in various positions of the AZ sequence. The probability of this sequence-independent +1 frameshifting increased in proportion to the length of the open reading frame. Furthermore, the +1 frameshifting was induced in some sequences other than the AZ gene in a polyamine-dependent manner. These findings suggest that polyamines have the potential to shift the reading frame in the +1 direction in any sequence. Finally, we showed that the probability of the sequence-independent +1 frameshifting by polyamines is likely inversely correlated with translation efficiency. Based on these results, we propose a model of the molecular mechanism for AZ +1 frameshifting.

中文翻译：

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翻译效率影响多胺与序列无关的+1核糖体移码。

抗酶（AZ）与鸟氨酸脱羧酶相互作用，催化多胺生物合成的第一步并将其募集到蛋白酶体中进行降解。合成功能性AZ蛋白需要在终止密码子处转变阅读框。这种编程的+1核糖体移码是由多胺引起的，但是分子机制仍然未知。在这项研究中，我们探索了使用人类无细胞翻译系统的多胺依赖性+1移码机制。出乎意料的是，亚精胺诱导突变体中的+1移码，将突变位点的终止密码子替换为有义密码子。截断实验表明+1移码在AZ序列的各个位置混杂发生。这种与序列无关的+1移码的可能性与开放阅读框的长度成比例地增加。此外，在除AZ基因以外的一些序列中以多胺依赖性方式诱导+1移码。这些发现表明，多胺具有以任何顺序在+1方向上移动阅读框的潜力。最后，我们证明了多胺与序列无关的+1移码的可能性可能与翻译效率成反比。基于这些结果，我们提出了AZ +1移码的分子机制模型。这些发现表明，多胺具有以任何顺序在+1方向上移动阅读框的潜力。最后，我们证明了多胺与序列无关的+1移码的可能性可能与翻译效率成反比。基于这些结果，我们提出了AZ +1移码的分子机制模型。这些发现表明，多胺具有以任何顺序在+1方向上移动阅读框的潜力。最后，我们证明了多胺与序列无关的+1移码的可能性可能与翻译效率成反比。基于这些结果，我们提出了AZ +1移码的分子机制模型。