A novel interaction between G{beta}{gamma} and RNA polymerase II regulates cardiac fibrosis.

G{beta}{gamma} subunits are involved in an array of distinct signalling processes in various compartments of the cell, including the nucleus. To gain further insight into the functions of G{beta}{gamma} complexes, we investigated the functional role of G{beta}{gamma} signalling in the regulation of signal-responsive gene expression in primary cardiac fibroblasts. Here, we demonstrate that, following activation of the angiotensin type I receptor, G{beta}{gamma} dimers interact with RNA polymerase II (RNAPII) to directly regulate transcription of fibrotic genes. This interaction was specific for complexes containing the G{beta}1 subtype and preferentially occurred with the elongating form of RNAPII. The G{beta}{gamma}/RNAPII interaction was detected in multiple cell types in response to diverse signalling pathways, suggesting that it may be a general feature of signal-responsive transcriptional regulation. Taken together, our studies reveal a novel interaction between G{beta}{gamma} subunits and RNAPII, further shedding light on the diverse roles G{beta}{gamma} dimers play in cardiac fibrosis and in GPCR signalling.