DMA-tudor interaction modules control the specificity of in vivo condensates

• Published in: Cell Vol. 184; no. 14; pp. 3612 - 3625.e17
• Main Authors: Courchaine, Edward M., Barentine, Andrew E.S., Straube, Korinna, Lee, Dong-Ryoung, Bewersdorf, Joerg, Neugebauer, Karla M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.07.2021
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - metabolism; Biomolecular Condensates - metabolism; biomolecular condensation; Cajal body; Cell Nucleus - metabolism; Coiled Bodies - metabolism; condensates; dimethylarginine; DMA; Drosophila melanogaster - metabolism; HEK293 Cells; HeLa Cells; Humans; Ligands; membraneless organelle; Methylation; Mice; microscopy; MLO; Models, Biological; motor neurons; NIH 3T3 Cells; nuclear gem; organelles; post-translational modification; Protein Binding; Protein Domains; Protein Multimerization; Ribonucleoproteins, Small Nuclear - metabolism; SMN Complex Proteins - chemistry; SMN Complex Proteins - metabolism; tudor domains; MLO; biomolecular condensation; membraneless organelle; dimethylarginine; tudor domains; Cajal body; nuclear gem; DMA; post-translational modification
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2021.05.008

Biomolecular condensation is a widespread mechanism of cellular compartmentalization. Because the “survival of motor neuron protein” (SMN) is implicated in the formation of three different membraneless organelles (MLOs), we hypothesized that SMN promotes condensation. Unexpectedly, we found that SMN’s globular tudor domain was sufficient for dimerization-induced condensation in vivo, whereas its two intrinsically disordered regions (IDRs) were not. Binding to dimethylarginine (DMA) modified protein ligands was required for condensate formation by the tudor domains in SMN and at least seven other fly and human proteins. Remarkably, asymmetric versus symmetric DMA determined whether two distinct nuclear MLOs—gems and Cajal bodies—were separate or “docked” to one another. This substructure depended on the presence of either asymmetric or symmetric DMA as visualized with sub-diffraction microscopy. Thus, DMA-tudor interaction modules—combinations of tudor domains bound to their DMA ligand(s)—represent versatile yet specific regulators of MLO assembly, composition, and morphology. [Display omitted] •The tudor domain of SMN promotes condensation by binding dimethylarginine (DMA)•DMA-tudor condensation is a shared property of numerous other tudor domains•Each tudor domain has a specific dependence on symmetric or asymmetric DMA•aDMA and sDMA levels define the composition and substructure of Cajal bodies The SMN tudor domain is sufficient for condensation by binding to dimethylarginine (DMA) modified protein ligands. Asymmetric versus symmetric DMA determines whether gems and Cajal bodies were separate or “docked” to one another.