Although actin is well known as a key cytoskeletal protein, it has also been linked to a number of nuclear processes. However, many of its functions within the nucleus have remained poorly understood. To shed light on the nuclear functions of actin, Maria Vartiainen and co-workers (Viita et al., 2019) investigate the nuclear interactome of actin. By using two complementary mass spectrometry-based approaches – affinity purification to detect stable partners and BioID to identify transient interactors – they show that actin binds chromatin remodellers and modifiers, as well as proteins involved in transcription and mRNA processing. One novel interactor of actin is the histone acetyl transferase (HAT) human Ada-Two-A containing (hATAC) complex. The authors verify the interaction of actin with the hATAC subunit KAT14 by co-immunoprecipitation and discover that KAT14 shows preferential binding for a non-polymerising actin mutant, indicating that hATAC preferentially interacts with monomeric actin. Furthermore, they find that actin interacts with the C-terminal region of KAT14, suggesting that actin modulates the HAT activity that is contained in this portion of the protein. Indeed, they show that actin decreases the ability of KAT14 to acetylate histone H4K5 both in vitro and in vivo. Additionally, the authors investigate the role of actin in alternative splicing. Surprisingly, they find that both increased and decreased levels of nuclear actin change exon inclusion in reporters that typically show low exon inclusion levels. Taken together, these findings indicate that actin modulates a number of important nuclear process and also provide a resource to study its non-cytoskeletal functions in more detail.
