Chromatin meets condensates: emerging interplays linking nuclear paraspeckles to gene activation

Nuclear paraspeckles are membrane-less protein-protein and protein-RNA condensates that assemble co-transcriptionally upon the expression of long non-coding RNA NEAT1. While efforts in the past two decades extensively characterized the components and structures of nuclear paraspeckles, their biochemical, cellular, and physiological functions remain largely unclear. Emerging evidence has revealed that paraspeckles physically interact with active chromatin and promote its establishment, implicating the role of paraspeckles as a functional hub to maintain the active state of chromatin. Here, we discuss recent advances and key knowledge gaps in the biology of paraspeckles, including their interplay with active chromatin, disease associated mutations, and functional discrepancies between mouse and human systems.