Sep 15, 2017

Kinetochore inactivation by expression of a repressive mRNA

ELife
Jingxun ChenElçin Ünal

Abstract

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.

  • References66
  • Citations8

Mentioned in this Paper

Saccharomyces cerevisiae Proteins
RNA Isoforms
Transcription, Genetic
Yeasts
Gene Expression Regulation, Fungal
Protein Biosynthesis
Gene Expression
Cell Differentiation Process
Microtubules
TID3 protein, S cerevisiae

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