Kinetochore inactivation by expression of a repressive mRNA
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/27417 |
| _version_ | 1811200301163610112 |
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| author | Jingxun Chen Amy Tresenrider Minghao Chia David T McSwiggen Gianpiero Spedale Victoria Jorgensen Hanna Liao Folkert Jacobus van Werven Elçin Ünal |
| author_facet | Jingxun Chen Amy Tresenrider Minghao Chia David T McSwiggen Gianpiero Spedale Victoria Jorgensen Hanna Liao Folkert Jacobus van Werven Elçin Ünal |
| author_sort | Jingxun Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:01:20Z |
| format | Article |
| id | doaj.art-7480204f0f8649d9832e1dee6c5fdc69 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:01:20Z |
| publishDate | 2017-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7480204f0f8649d9832e1dee6c5fdc692022-12-22T03:52:39ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.27417Kinetochore inactivation by expression of a repressive mRNAJingxun Chen0Amy Tresenrider1Minghao Chia2David T McSwiggen3Gianpiero Spedale4Victoria Jorgensen5Hanna Liao6Folkert Jacobus van Werven7https://orcid.org/0000-0002-6685-2084Elçin Ünal8https://orcid.org/0000-0002-6768-609XDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesThe Francis Crick Institute, London, United KingdomDepartment of Molecular and Cell Biology, Li Ka Shing Center, University of California, Berkeley, Berkeley, United StatesThe Francis Crick Institute, London, United KingdomDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesThe Francis Crick Institute, London, United KingdomDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; The Paul F. Glenn Center for Aging Research, University of California, Berkeley, Berkeley, United StatesDifferentiation 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.https://elifesciences.org/articles/27417meiosiskinetochoregene regulationuORF translationbudding yeasttranscription |
| spellingShingle | Jingxun Chen Amy Tresenrider Minghao Chia David T McSwiggen Gianpiero Spedale Victoria Jorgensen Hanna Liao Folkert Jacobus van Werven Elçin Ünal Kinetochore inactivation by expression of a repressive mRNA eLife meiosis kinetochore gene regulation uORF translation budding yeast transcription |
| title | Kinetochore inactivation by expression of a repressive mRNA |
| title_full | Kinetochore inactivation by expression of a repressive mRNA |
| title_fullStr | Kinetochore inactivation by expression of a repressive mRNA |
| title_full_unstemmed | Kinetochore inactivation by expression of a repressive mRNA |
| title_short | Kinetochore inactivation by expression of a repressive mRNA |
| title_sort | kinetochore inactivation by expression of a repressive mrna |
| topic | meiosis kinetochore gene regulation uORF translation budding yeast transcription |
| url | https://elifesciences.org/articles/27417 |
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