Unveiling the intricacies of paraspeckle formation and function

Paraspeckle nuclear bodies form when the NEAT1 long noncoding RNA is transcribed and bound by multiple RNA-binding proteins. First described 20 years ago, in recent years a growing appreciation of paraspeckle dynamics has led to new understandings, in both structure and function. Structurally, paraspeckles form via distinct physico-chemical domains arising from the composition of key proteins, recruited to different parts of NEAT1. These domains interact, creating a core–shell structured paraspeckle via microphase separation. Functionally, many environmental, chemical, and mechanical triggers can alter paraspeckle abundance, with important consequences depending on the cell type, developmental stage, and trigger identity. Underpinning these insights are new tools for paraspeckle research, including screening assays, proximity-based identification tools, and RNA processing modulators. A picture is emerging of paraspeckles as gene regulatory condensates in many healthy and disease settings. Critically, however, paraspeckle functional importance is generally most apparent when cells and organisms face external stressors.