Differentiation programs such as meiosis depend on extensive gene regulation to mediate cellular morphogenesis. Meiosis requires transient removal of the outer kinetochore, the complex that connects microtubules to chromosomes. How the meiotic gene expression program temporally restricts kinetochore function is unknown. We discovered that in budding yeast, kinetochore inactivation occurs by reducing the abundance of a limiting subunit, Ndc80. Furthermore, we uncovered an integrated mechanism that acts at the transcriptional and translational level to repress NDC80 expression. Central to this mechanism is the developmentally controlled transcription of an alternate NDC80 mRNA isoform, which itself cannot produce protein due to regulatory upstream ORFs in its extended 5' leader. Instead, transcription of this isoform represses the canonical NDC80 mRNA expression in cis, thereby inhibiting Ndc80 protein synthesis. This model of gene regulation raises the intriguing notion that transcription of an mRNA, despite carrying a canonical coding sequence, can directly cause gene repression.

诸如减数分裂的分化程序依赖于广泛的基因调节来介导细胞形态发生。减数分裂需要暂时去除外部的动粒，复合物将微管连接到染色体。减数分裂基因表达程序如何在时间上限制线粒体功能尚不清楚。我们发现在发芽酵母中，通过减少限制性亚基Ndc80的丰度，发生了线粒体失活。此外，我们发现了一种在转录和翻译水平上抑制NDC80表达的整合机制。该机制的中心是替代NDC80的受发育控制的转录mRNA亚型，由于扩展的5'前导序列中上游的ORF调控，自身不能产生蛋白质。而是，此同工型的转录抑制顺式规范的NDC80 mRNA表达，从而抑制Ndc80蛋白的合成。这种基因调节模型提出了一个有趣的观点，即尽管带有标准的编码序列，但mRNA的转录仍可直接引起基因阻抑。