Abstract
The nuclear envelope (NE) is the hallmark of eukaryotic cells, serving as a critical physical barrier that compartmentalizes the genome and separates nuclear and cytoplasmic processes to tightly regulate nucleocytoplasmic transport. Biomolecular phase separation, a physicochemical process frequently driven by proteins containing intrinsically disordered regions (IDRs), is a fundamental mechanism governing diverse cellular activities. Yet, its roles at the nuclear envelope remain largely unexplored. In our recent study (Tang et al., Developmental Cell, 2025), we demonstrated how phase separation at the nuclear lamina (NL) orchestrates transcriptional responses to environmental stress in plants. Building on this finding, this commentary synthesizes the emerging insights into the contributions of phase separation across the entire NE, including the NL, nuclear pore complex (NPC) and nuclear membranes, in both plant and animal systems. Collectively, recent advances establish that perinuclear phase separation as a pivotal regulator of genome activity and nucleocytoplasmic transport. This commentary concludes by highlighting the imperative to further investigation into perinuclear phase separation as an essential and dynamic signaling hub that integrates cytoplasmic signals with nuclear responses to various cellular and environmental cues.
Keywords
Nuclear envelope, Nuclear membrane, Nuclear lamina, Nuclear pore complex, Phase separation, IDRs, Condensates