Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues.
The localization, mass, and dynamics of microtubules are important in many processes. Cells may actively monitor the state of their microtubules and respond to perturbation, but how this occurs outside mitosis is poorly understood. We used gene-expression analysis in quiescent cells to analyze respo...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-04-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000225 |
| _version_ | 1819124402530287616 |
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| author | Ivana Gasic Sarah A Boswell Timothy J Mitchison |
| author_facet | Ivana Gasic Sarah A Boswell Timothy J Mitchison |
| author_sort | Ivana Gasic |
| collection | DOAJ |
| description | The localization, mass, and dynamics of microtubules are important in many processes. Cells may actively monitor the state of their microtubules and respond to perturbation, but how this occurs outside mitosis is poorly understood. We used gene-expression analysis in quiescent cells to analyze responses to subtle and strong perturbation of microtubules. Genes encoding α-, β, and γ-tubulins (TUBAs, TUBBs, and TUBGs), but not δ- or ε-tubulins (TUBDs or TUBEs), exhibited the strongest differential expression response to microtubule-stabilizing versus destabilizing drugs. Quantitative PCR of exon versus intron sequences confirmed that these changes were caused by regulation of tubulin mRNA stability and not transcription. Using tubulin mRNA stability as a signature to query the Gene Expression Omnibus (GEO) database, we find that tubulin genes respond to toxins known to damage microtubules. Importantly, we find many other experimental perturbations, including multiple signaling and metabolic inputs that trigger tubulin differential expression, suggesting their novel, to our knowledge, role in the regulation of the microtubule cytoskeleton. Mechanistic follow-up confirms that one important physiological signal, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activity, indeed regulates tubulin mRNA stability via changes in microtubule dynamics. We propose that tubulin gene expression is regulated as part of many coordinated biological responses, with wide implications in physiology and toxicology. Furthermore, we present a new way to discover microtubule regulation using transcriptomics. |
| first_indexed | 2024-12-22T07:23:41Z |
| format | Article |
| id | doaj.art-798cc5e1b9df437eab4c73b4fd197399 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-22T07:23:41Z |
| publishDate | 2019-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-798cc5e1b9df437eab4c73b4fd1973992022-12-21T18:34:12ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-04-01174e300022510.1371/journal.pbio.3000225Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues.Ivana GasicSarah A BoswellTimothy J MitchisonThe localization, mass, and dynamics of microtubules are important in many processes. Cells may actively monitor the state of their microtubules and respond to perturbation, but how this occurs outside mitosis is poorly understood. We used gene-expression analysis in quiescent cells to analyze responses to subtle and strong perturbation of microtubules. Genes encoding α-, β, and γ-tubulins (TUBAs, TUBBs, and TUBGs), but not δ- or ε-tubulins (TUBDs or TUBEs), exhibited the strongest differential expression response to microtubule-stabilizing versus destabilizing drugs. Quantitative PCR of exon versus intron sequences confirmed that these changes were caused by regulation of tubulin mRNA stability and not transcription. Using tubulin mRNA stability as a signature to query the Gene Expression Omnibus (GEO) database, we find that tubulin genes respond to toxins known to damage microtubules. Importantly, we find many other experimental perturbations, including multiple signaling and metabolic inputs that trigger tubulin differential expression, suggesting their novel, to our knowledge, role in the regulation of the microtubule cytoskeleton. Mechanistic follow-up confirms that one important physiological signal, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) activity, indeed regulates tubulin mRNA stability via changes in microtubule dynamics. We propose that tubulin gene expression is regulated as part of many coordinated biological responses, with wide implications in physiology and toxicology. Furthermore, we present a new way to discover microtubule regulation using transcriptomics.https://doi.org/10.1371/journal.pbio.3000225 |
| spellingShingle | Ivana Gasic Sarah A Boswell Timothy J Mitchison Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. PLoS Biology |
| title | Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. |
| title_full | Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. |
| title_fullStr | Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. |
| title_full_unstemmed | Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. |
| title_short | Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. |
| title_sort | tubulin mrna stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues |
| url | https://doi.org/10.1371/journal.pbio.3000225 |
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