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Scientific article
Open access
English

Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues

Published inPLoS biology, vol. 17, no. 4, p. 1-23; e3000225
Publication date2019-04-09
First online date2019-04-09
Abstract

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.

eng
Affiliation Not a UNIGE publication
Funding
  • National Institutes of Health - [NIH P50 GM107618]
  • NIGMS NIH HHS - [P50 GM107618]
  • Damon Runyon Cancer Research Foundation - [DRG:2279-16]
Citation (ISO format)
GASIC, Ivana, BOSWELL, Sarah A., MITCHISON, Timothy J. Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues. In: PLoS biology, 2019, vol. 17, n° 4, p. 1–23. doi: 10.1371/journal.pbio.3000225
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Article (Published version)
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ISSN of the journal1544-9173
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