Tudor-dimethylarginine interactions: the condensed version.

Biomolecular condensates (BMCs) can facilitate or inhibit diverse cellular functions. BMC formation is driven by noncovalent protein-protein, protein-RNA, and RNA-RNA interactions. Here, we focus on Tudor domain-containing proteins - such as survival motor neuron protein (SMN) - that contribute to BMC formation by binding to dimethylarginine (DMA) modifications on protein ligands. SMN is present in RNA-rich BMCs, and its absence causes spinal muscular atrophy (SMA). SMN's Tudor domain forms cytoplasmic and nuclear BMCs, but its DMA ligands are largely unknown, highlighting open questions about the function of SMN. Moreover, DMA modification can alter intramolecular interactions and affect protein localization. Despite these emerging functions, the lack of direct methods of DMA detection remains an obstacle to understanding Tudor-DMA interactions in cells.

The coilin N-terminus mediates multivalent interactions between coilin and Nopp140 to form and maintain Cajal bodies.

Cajal bodies (CBs) are ubiquitous nuclear membraneless organelles (MLOs) that concentrate and promote efficient biogenesis of snRNA-protein complexes involved in splicing (snRNPs). Depletion of the CB scaffolding protein coilin disperses snRNPs, making CBs a model system for studying the structure and function of MLOs. Although it is assumed that CBs form through condensation, the biomolecular interactions responsible remain elusive. Here, we discover the unexpected capacity of coilin's N-terminal domain (NTD) to form extensive fibrils in the cytoplasm and discrete nuclear puncta in vivo. Single amino acid mutational analysis reveals distinct molecular interactions between coilin NTD proteins to form fibrils and additional NTD interactions with the nuclear Nopp140 protein to form puncta. We provide evidence that Nopp140 has condensation capacity and is required for CB assembly. From these observations, we propose a model in which coilin NTD-NTD mediated assemblies make multivalent contacts with Nopp140 to achieve biomolecular condensation in the nucleus.