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

Gβγ 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 Gβγ complexes, we investigated the functional role of Gβγ 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, Gβγ dimers interact with RNA polymerase II (RNAPII) to directly regulate transcription of fibrotic genes. This interaction was specific for complexes containing the Gβ1 subtype and preferentially occurred with the elongating form of RNAPII. The Gβγ/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 Gβγ subunits and RNAPII, further shedding light on the diverse roles Gβγ dimers play in cardiac fibrosis and in GPCR signalling.