Paraspeckles: Where Long Noncoding RNA Meets Phase Separation

Paraspeckles have become an important model system for studying long noncoding RNA–protein interactions in the context of gene regulation. Nascent 23 000-nucleotide NEAT1 long noncoding RNA transcripts act as a seed to recruit nuclear RNA-binding proteins and build a paraspeckle. Protein domains that mediate liquid–liquid phase separation are essential for many aspects of paraspeckle formation, including gluing together individual ribonucleoprotein bundles into a mature paraspeckle. Paraspeckle formation is dynamic and triggered by many different cell stress scenarios including infection and transformation. Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles – protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA–protein and protein–protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings. Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles – protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA–protein and protein–protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings.