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The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via α-TAT1 gene expression

AuthorsFernández-Barrera, Jaime ; Bernabé-Rubio, Miguel ; Casares-Arias, Javier ; Rangel, Laura ; Fernández-Martín, Laura; Correas, Isabel ; Alonso, Miguel A.
Issue Date20-Jul-2018
CitationJournal of Cell Biology 217: 929- 944 (2018)
AbstractThe role of formins in microtubules is not well understood. In this study, we have investigated the mechanism by which INF2, a formin mutated in degenerative renal and neurological hereditary disorders, controls microtubule acetylation. We found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired myocardin-related transcription factor (MRTF)/serum response factor (SRF)- dependent transcription, which is known to be repressed by increased levels of G-actin. The effect on tubulin acetylation was caused by the almost complete absence of α-tubulin acetyltransferase 1 (α-TAT1) messenger RNA (mRNA). Activation of the MRTF-SRF transcriptional complex restored α-TAT1 mRNA levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements were consistently identified in the α-TAT1 gene. The effect of INF2 silencing on microtubule acetylation was also observed in epithelial ECV304 cells, but not in Jurkat T cells. Therefore, the actin-MRTF-SRF circuit controls α-TAT1 transcription. INF2 regulates the circuit, and hence microtubule acetylation, in cell types where it has a prominent role in actin polymerization.
Identifiersdoi: 10.1083/jcb.201702157
issn: 1540-8140
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