Framework to function: Mechanosensitive regulators of gene transcription

Mechanobiology has shifted our understanding of fundamental cellular and physiological functions. Changes to the stiffness of the extracellular matrix, cell rigidity, or shape of the cell environment were considered in the past to be a consequence of aging or pathological processes. We now understand that these factors can actually be causative biological mediators of cell growth to control organ size. Mechanical cues are known to trigger a relatively fast translocation of specific transcriptional co-factors such as MRTFs, YAP and TAZ from the cytoplasm to the cell nucleus to initiate discrete transcriptional programs. The focus of this review is the molecular mechanisms by which biophysical stimuli that induce changes in cytoplasmic actin dynamics are communicated within cells to elicit gene-specific transcription via nuclear localisation or activation of specialized transcription factors, namely MRTFs and the Hippo pathway effectors YAP and TAZ. We propose here that MRTFs, YAP and TAZ closely collaborate as mechano-effectors.