Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay
Abstract Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport, and power cell division. The concentration of αβ-tubulins is tightly controlled through a posttranscriptional mechanism involving selective and regulated degradation of tubulin-e...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54036-0 |
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| author | Alina Batiuk Markus Höpfler Ana C. Almeida Deryn Teoh En-Jie Oscar Vadas Evangelia Vartholomaiou Ramanujan S. Hegde Zhewang Lin Ivana Gasic |
| author_facet | Alina Batiuk Markus Höpfler Ana C. Almeida Deryn Teoh En-Jie Oscar Vadas Evangelia Vartholomaiou Ramanujan S. Hegde Zhewang Lin Ivana Gasic |
| author_sort | Alina Batiuk |
| collection | DOAJ |
| description | Abstract Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport, and power cell division. The concentration of αβ-tubulins is tightly controlled through a posttranscriptional mechanism involving selective and regulated degradation of tubulin-encoding mRNAs. Degradation is initiated by TTC5, which recognizes tubulin-synthesizing ribosomes and recruits downstream effectors to trigger mRNA deadenylation. Here, we investigate how cells regulate TTC5 activity. Biochemical and structural proteomic approaches reveal that under normal conditions, soluble αβ-tubulins bind to and sequester TTC5, preventing it from engaging nascent tubulins at translating ribosomes. We identify the flexible C-terminal tail of TTC5 as a molecular switch, toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss of sequestration by soluble αβ-tubulins constitutively activates TTC5, leading to diminished tubulin mRNA levels and compromised microtubule-dependent chromosome segregation during cell division. Our findings provide a paradigm for how cells regulate the activity of a specificity factor to adapt posttranscriptional regulation of gene expression to cellular needs. |
| format | Article |
| id | doaj-art-1a756e023ff8410f80970d5b868ba400 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1a756e023ff8410f80970d5b868ba4002024-11-24T12:33:41ZengNature PortfolioNature Communications2041-17232024-11-0115111410.1038/s41467-024-54036-0Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decayAlina Batiuk0Markus Höpfler1Ana C. Almeida2Deryn Teoh En-Jie3Oscar Vadas4Evangelia Vartholomaiou5Ramanujan S. Hegde6Zhewang Lin7Ivana Gasic8Department of Molecular and Cellular Biology, University of GenevaMedical Research Council Laboratory of Molecular BiologyDepartment of Molecular and Cellular Biology, University of GenevaDepartment of Biological Sciences, National University of SingaporeProteins, Peptides and RNA to Protein Core Facility, Faculty of Medicine, University of GenevaDepartment of Molecular and Cellular Biology, University of GenevaMedical Research Council Laboratory of Molecular BiologyDepartment of Biological Sciences, National University of SingaporeDepartment of Molecular and Cellular Biology, University of GenevaAbstract Microtubules, built from heterodimers of α- and β-tubulins, control cell shape, mediate intracellular transport, and power cell division. The concentration of αβ-tubulins is tightly controlled through a posttranscriptional mechanism involving selective and regulated degradation of tubulin-encoding mRNAs. Degradation is initiated by TTC5, which recognizes tubulin-synthesizing ribosomes and recruits downstream effectors to trigger mRNA deadenylation. Here, we investigate how cells regulate TTC5 activity. Biochemical and structural proteomic approaches reveal that under normal conditions, soluble αβ-tubulins bind to and sequester TTC5, preventing it from engaging nascent tubulins at translating ribosomes. We identify the flexible C-terminal tail of TTC5 as a molecular switch, toggling between soluble αβ-tubulin-bound and nascent tubulin-bound states. Loss of sequestration by soluble αβ-tubulins constitutively activates TTC5, leading to diminished tubulin mRNA levels and compromised microtubule-dependent chromosome segregation during cell division. Our findings provide a paradigm for how cells regulate the activity of a specificity factor to adapt posttranscriptional regulation of gene expression to cellular needs.https://doi.org/10.1038/s41467-024-54036-0 |
| spellingShingle | Alina Batiuk Markus Höpfler Ana C. Almeida Deryn Teoh En-Jie Oscar Vadas Evangelia Vartholomaiou Ramanujan S. Hegde Zhewang Lin Ivana Gasic Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay Nature Communications |
| title | Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay |
| title_full | Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay |
| title_fullStr | Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay |
| title_full_unstemmed | Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay |
| title_short | Soluble αβ-tubulins reversibly sequester TTC5 to regulate tubulin mRNA decay |
| title_sort | soluble αβ tubulins reversibly sequester ttc5 to regulate tubulin mrna decay |
| url | https://doi.org/10.1038/s41467-024-54036-0 |
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