Paraspeckles are subnuclear bodies that form when a specific group of nuclear RNA binding proteins are brought into close proximity by binding the long noncoding RNA, NEAT1, through a process of liquid-liquid phase condensation. This process of paraspeckle formation is coordinated and dynamic, with a high nuclear concentration of soluble paraspeckle proteins ‘poised’ to condense onto NEAT1 as soon as it is transcribed.
Proteins that build paraspeckles are enriched in a type of intrinsically disordered domain termed the ‘prion like domain’ including FUS and HNRNPA1. We have been carrying out studies in vitro to characterise the biophysical properties of proteins required for paraspeckle formation in order to learn more about mechanisms involved. In addition to gel- and liquid-formation assays and crystallographic studies, we have also been using small-angle neutron scattering to seek structural detail on the essential paraspeckle protein HNRNPK which forms a variety of aggregates, droplets and fibrils when made recombinantly. These insights have helped us build a better understanding of the dynamics and molecular structure of paraspeckle components.