Kinetochore inactivation by expression of a repressive mRNA
| Autor: | Hanna Liao, Jingxun Chen, Amy Tresenrider, Victoria Jorgensen, Gianpiero Spedale, David T. McSwiggen, Folkert J. van Werven, Minghao Chia, Elçin Ünal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene isoform chromosomes Saccharomyces cerevisiae Proteins QH301-705.5 1.1 Normal biological development and functioning Science S. cerevisiae Saccharomyces cerevisiae Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Genetic Transcription (biology) Underpinning research Gene expression RNA Isoforms Genetics Coding region meiosis budding yeast uORF translation Biology (General) Kinetochores genes Gene Regulation of gene expression General Immunology and Microbiology Kinetochore General Neuroscience Nuclear Proteins General Medicine kinetochore NDC80 030104 developmental biology Fungal Gene Expression Regulation Protein Biosynthesis Medicine Generic health relevance Biochemistry and Cell Biology gene regulation transcription 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | eLife, Vol 6 (2017) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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