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.

中文翻译：

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通过表达抑制性 mRNA 使动粒失活

减数分裂等分化程序依赖于广泛的基因调控来介导细胞形态发生。减数分裂需要暂时去除外着丝粒，即连接微管和染色体的复合体。减数分裂基因表达程序如何暂时限制着丝粒功能尚不清楚。我们发现，在芽殖酵母中，着丝粒失活是通过减少限制亚基 Ndc80 的丰度而发生的。此外，我们发现了一种在转录和翻译水平上发挥作用以抑制 NDC80 表达的整合机制。该机制的核心是另一种 NDC80 mRNA 亚型的发育控制转录，由于其延伸的 5' 前导序列中的上游 ORF 受到调节，该亚型本身无法产生蛋白质。相反，该异构体的转录会抑制典型的 NDC80 mRNA 顺式表达，从而抑制 Ndc80 蛋白合成。这种基因调控模型提出了一个有趣的概念，即 mRNA 的转录尽管携带规范的编码序列，但可以直接导致基因抑制。