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An interaction between Gβγ and RNA polymerase II regulates transcription in cardiac fibroblasts

ABSTRACT: Gβγ subunits are involved in an array of different signalling processes in various compartments of the cell, including the nucleus. To gain further insight into the functions of nuclear Gβγ, we investigated the functional role of Gβγ signalling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Here, we demonstrate that following activation of the angiotensin II type I receptor in these cells, Gβγ dimers interact with RNA polymerase II (RNAPII). Our findings suggest that Gβ1 recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. The Gβγ-RNAPII interaction was also investigated in HEK 293 cells and was regulated by signaling pathways that diverged from those operating in cardiac fibroblasts, suggesting that although it may be a conserved feature of transcriptional regulation, such regulation may be cell-specific. Taken together, our studies reveal a novel interaction between Gβγ subunits and RNA polymerase II and expand the role for Gβγ signalling in cardiac fibrosis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE147416 | GEO | 2023/02/09

REPOSITORIES: GEO

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