Protein and RNA interactions of low-complexity domains and their role in the formation of nuclear bodies

In eukaryotic cells, numerous nuclear bodies (NBs) form through condensation (Boeynaems et al., 2018). NBs are protein-enriched dynamic protein hubs that mediate cellular processes from gene expression to DNA repair and signal transduction (Morimoto & Boerkoel, 2013). Proteins targeted to NBs typically contain intrinsically disordered low-complexity domains (LCDs) that are proposed to drive condensation. Strikingly, the amino acid bias of these LCDs differs depending on the subcellular localization of the proteins, raising the question of whether characteristic LCDs are one possibility to direct NB targeting (Wang et al., 2018). In the current project, we intend to investigate the fundamental principles that preserve the NB’s identity in their cellular environment by focusing on splicing speckles and paraspeckles, which are often located nearby. Although both types of speckles have been described to be liquid-like in terms of the diffusive properties of proteins (Weber, 2019), they likewise display a core-shell or micellar protein-RNA assembly (Yamazaki et al., 2021; Fei et al., 2017). The latter arises from the interplay of favorable sequence-encoded molecular interactions of proteins and RNAs. Notably, co-localized non-coding RNAs (ncRNAs) and RNA-binding proteins (RBPs) regulate a variety of important cellular processes (Morimoto & Boerkoel, 2013) and are often deregulated in pathologies, as seen for splicing speckle components (MALAT1 and SRSF1) and paraspeckle components (NEAT1 and NONO) in cancer (Kessler et al., 2019; Malakar et al., 2017). Hence, a close investigation of the assembly of NBs could also prove useful to understand the role of protein and RNA interaction in the pathological context.