The article by Olson and Nordheim explores the link between actin dynamics and gene transcription in driving cellular motile functions. It highlights the role of myocardin-related transcription factor (MRTF) and serum response factor (SRF) in this process. The authors review how actin polymerization liberates MRTF cofactors, which then activate SRF to modulate the expression of genes encoding structural and regulatory effectors of actin dynamics. This insight has led to further research into the actin–MRTF–SRF circuit and alternative mechanisms linking cytoskeletal dynamics and genome activity. The review discusses various cellular receptors that respond to motility-inducing signals and activate Rho family GTPases, which regulate actin polymerization. It also examines the signaling pathways that communicate actin dynamics to the nucleus, including G protein-coupled receptors, receptor tyrosine kinases, integrins, TGFβ, and E-cadherin signaling. The article further explores the role of nuclear actin and ABPs in modulating gene expression and the involvement of non-canonical Wnt signaling in actin dynamics. The authors highlight the importance of the MRTF–SRF circuit in regulating muscle-specific and contractile genes, as well as genes affecting actin dynamics and cell motility. They also discuss the role of miRNAs in controlling MRTF–SRF activity and the implications of this pathway in cardiovascular diseases and cancer. Finally, the authors conclude by emphasizing the need for further research to understand the molecular details of the MRTF–SRF circuit and its role in various cellular processes.The article by Olson and Nordheim explores the link between actin dynamics and gene transcription in driving cellular motile functions. It highlights the role of myocardin-related transcription factor (MRTF) and serum response factor (SRF) in this process. The authors review how actin polymerization liberates MRTF cofactors, which then activate SRF to modulate the expression of genes encoding structural and regulatory effectors of actin dynamics. This insight has led to further research into the actin–MRTF–SRF circuit and alternative mechanisms linking cytoskeletal dynamics and genome activity. The review discusses various cellular receptors that respond to motility-inducing signals and activate Rho family GTPases, which regulate actin polymerization. It also examines the signaling pathways that communicate actin dynamics to the nucleus, including G protein-coupled receptors, receptor tyrosine kinases, integrins, TGFβ, and E-cadherin signaling. The article further explores the role of nuclear actin and ABPs in modulating gene expression and the involvement of non-canonical Wnt signaling in actin dynamics. The authors highlight the importance of the MRTF–SRF circuit in regulating muscle-specific and contractile genes, as well as genes affecting actin dynamics and cell motility. They also discuss the role of miRNAs in controlling MRTF–SRF activity and the implications of this pathway in cardiovascular diseases and cancer. Finally, the authors conclude by emphasizing the need for further research to understand the molecular details of the MRTF–SRF circuit and its role in various cellular processes.