A novel interaction between Gβγ and RNA polymerase II regulates cardiac fibrosis.

Khan, S. M.; Martin, R. D.; Bouazza, C.; Jones-Tabah, J.; Zhang, A.; MacKinnon, S.; Trieu, P.; Gora, S.; Clarke, P. B.; Tanny, J. C.; Hebert, T. E.

doi:10.1101/415935

bioRxiv · 10.1101/415935

A novel interaction between Gβγ and RNA polymerase II regulates cardiac fibrosis.

Khan, S. M.·Martin, R. D.·Bouazza, C.·Jones-Tabah, J.·Zhang, A.·MacKinnon, S.·Trieu, P.·Gora, S.·Clarke, P. B.·Tanny, J. C.·Hebert, T. E.

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Abstract

G{beta}{gamma} subunits are involved in many different signalling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear G{beta}{gamma}, we investigated the functional role of G{beta}{gamma} signalling in regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Following activation of the angiotensin II type I receptor in these cells, G{beta}{gamma} dimers interact with RNA polymerase II (RNAPII). Our findings suggest that G{beta}1 recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. The interaction between G{beta}{gamma} subunits and RNAPII expands the role for G{beta}{gamma} signalling in cardiac fibrosis. The G{beta}{gamma}-RNAPII interaction was regulated by signaling pathways in HEK 293 cells that diverged from those operating in cardiac fibroblasts. Thus, the interaction may be a conserved feature of transcriptional regulation although such regulation may be cell-specific.

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Khan, S. M., Martin, R. D., Bouazza, C., Jones-Tabah, J., Zhang, A., MacKinnon, S., Trieu, P., Gora, S., Clarke, P. B., Tanny, J. C., Hebert, T. E.. 2018-09-13. A novel interaction between Gβγ and RNA polymerase II regulates cardiac fibrosis.. https://doi.org/10.1101/415935

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