Nuclear Actin

Abstract

Abstract While actin is a highly evolutionarily conserved protein that has been extensively studied for its role in the cytoskeleton, it also localises and functions within the nucleus. Tight regulation of both the level and form (monomeric vs filamentous) of nuclear actin is essential for many nuclear processes. Nuclear actin regulates transcription at multiple steps, including initiation, elongation and messenger ribonucleic acid (mRNA) processing. It also regulates chromatin organisation by controlling chromatin modifiers and mediating chromatin movement during transcription, deoxyribonucleic acid (DNA) repair and DNA replication. Finally, nuclear actin is a critical component of the nucleoskeleton, where it regulates nuclear structure and organisation, cellular response to mechanical signalling and nucleolar structure and function. These functions of nuclear actin are critical for maintaining cellular homeostasis, responding to cellular stress and mediating cell fate decisions. Key Concepts Different forms of nuclear actin regulate distinct aspects of transcription: G‐actin promotes the initiation of transcription and mediates the escape from pausing, whereas dynamic actin polymerisation is required for transcriptional elongation. Nuclear G‐actin acts as a scaffold to regulate the entire RNA biogenesis pathway from initiating transcription to translation. Both cytoplasmic and nuclear actin dynamics regulate SRF/MAL‐dependent transcription. Nuclear G‐actin directly interacts with histone modifiers and chromatin remodelling complexes to regulate chromatin accessibility for transcription, DNA repair and replication. Nuclear actin plays critical roles in the repair of DNA double‐strand breaks both by regulating chromatin remodelling complex activity and by F‐actin‐dependent chromatin movement or stabilisation of repair machinery. Nuclear F‐actin is also required for moving chromatin to and maintaining transcription factors and mediating DNA replication and chromosome segregation. Mechanotransduction impacts the nucleoskeleton to regulate the level and form of nuclear actin to mediate changes in transcription and chromatin organisation that drive the cell‐specific response to force. Actin localises and functions within the nucleolus and may mediate the nucleolar stress response. Tight regulation of nuclear actin level and/or polymerisation plays critical roles in cell fate transitions.