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

ABSTRACT: The 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 ?-tubulin acetyltransferase 1 (?-TAT1) messenger RNA (mRNA). Activation of the MRTF-SRF transcriptional complex restored ?-TAT1 mRNA levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements were consistently identified in the ?-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 ?-TAT1 transcription. INF2 regulates the circuit, and hence microtubule acetylation, in cell types where it has a prominent role in actin polymerization.

SUBMITTER: Fernandez-Barrera J 

PROVIDER: S-EPMC5839776 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature