The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2⁺ and mad3⁺, their short mRNA half-lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1⁺ mRNA has a short half-life despite a higher frequency of optimal codons, and despite the lack of known RNA-destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.

中文翻译：

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有丝分裂检查点基因表达通过密码子使用偏差进行调整


有丝分裂检查点（也称为纺锤体组装检查点，SAC）是保障染色体正确分离的信号通路。 SAC 的正确功能取决于足够的蛋白质浓度和 SAC 蛋白质之间适当的化学计量。然而，人们对 SAC 基因表达的调控知之甚少。在这里，我们在裂殖酵母裂殖酵母中证明，短 mRNA 半衰期和长蛋白质半衰期的组合支持稳定的 SAC 蛋白质水平。对于 SAC 基因mad2 ⁺和mad3 ⁺ ，它们的 mRNA 半衰期短部分是由高频率的非最佳密码子引起的。相比之下，尽管最佳密码子的频率较高，并且缺乏已知的 RNA 不稳定基序，但mad1 ⁺ mRNA 的半衰期较短。因此，不同的SAC基因采用不同的表达策略。我们进一步表明，Mad1 同二聚体通过共翻译形成，这可能需要某种密码子使用模式。综上所述，我们建议对 SAC 基因的密码子使用进行微调，以确保正确的 SAC 功能。我们的工作揭示了促进纺锤体组装检查点功能的基因表达特征，并表明同义突变可能会削弱检查点。