Design and principles of nuclear structure

The study of the eukaryotic cell nucleus is more relevant than ever. Nuclear organization is increasingly recognized as a key player in physiological processes such as differentiation and defects in nuclear organization are linked to many diseases. Understanding the functional architecture of the cell nucleus in relation to both the nuclear envelope and the organization of the genome is a major challenge. During gene expression, multiple regulatory steps make sure that alterations of chromatin structure are synchronized with RNA synthesis, cotranscriptional assembly of ribonucleoprotein complexes, transport to the cytoplasm and localized translation. These events are controlled by large multiprotein complexes or molecular machines, which are highly specialized and dynamic. Following the huge advances in the molecular understanding of some of these machineries, we are now faced with the problem of understanding how these molecular machines dynamically interact with the genome. It is evident that the nuclear lamina plays a central organizational role. Actin and actin binding proteins have also emerged as key players, regulating both chromosome organization and gene activity. In the cell nucleus actin interacts with many different proteins. These proteins include classical nuclear factors involved in chromatin structure and function, transcription and RNA processing as well as proteins that are normally involved in controlling the actin cytoskeleton in the cytoplasm. The promiscuity in the spectrum of protein-protein interactions correlates well with the conformational plasticity of actin, with the ability to undergo regulated changes in its polymerization states and the involvement of actomyosin motor complexes at the gene level. Several factors that control actin polymerization have been shown to localize in the nucleus, where they may regulate gene activity. Very recent data have provided the first visual evidence of polymerized nuclear actin. However many questions are still unresolved, including the mechanisms underlying nuclear actin polymerization, the possible involvement and regulation of distinct actomyosin complexes in specific nuclear functions and their regulation by signalling pathways and throughout the cell cycle. Emerging evidence also suggests that nuclear actin-based mechanisms have implications in nuclear reprogramming and disease. The time is now ripe to expand on the scope of actin-based mechanisms and place them in the context of nuclear dynamics.