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

Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

“…We demonstrated that the methylarginine-containing proteins were also more likely to be found in the nucleus and directly bind RNA; these features are commonly enriched in proteins driving LLPS and molecular condensates ( Ditlev et al., 2018 ). Given the striking enrichment of methylarginine in RNA processing, the influence of methylarginine on LLPS ( Courchaine et al., 2021 ; Hofweber et al., 2018 ; Qamar et al., 2018 ; Tsang et al., 2019 ), and the abundant literature on how LLPS is critical for nuclear function ( Strom and Brangwynne, 2019 )—together with the gross transcriptomic changes promoted by PRMT inhibition—it is tempting to hypothesize that methylarginine broadly regulates gene expression through LLPS. Future studies are needed to directly test this hypothesis.…”

Coilin oligomerization and remodeling by Nopp140 reveals a hybrid assembly mechanism for Cajal bodies

“…We speculate that this immobile coilin fraction is contained in longer-lived oligomers. Recent sub-diffraction fluorescence imaging has shown that CB morphology includes indentations or pockets to which other nuclear MLOs, such as gems, can be docked 30 . How coilin oligomers accommodate or facilitate these morphological relationships remains to be determined.…”

“…Untreated HeLa cells contain ~2 coilin-positive CBs per nucleus and slightly fewer SMN-containing MLOs, called gems. Gems lack coilin and do not overlap CBs, although they can be closely associated with CBs 30,40 . As a positive control, coilin depletion reduced the number of CBs to less than half the original number per nucleus without affecting the number of gems, as expected (Figs 2b-e).…”

“…One possibility is that coilin, which has an IDR linking the NTD with the structured CTD 31 , undergoes biomolecular condensation in addition to oligomerization through the NTD (Fig 6a). We tested this possibility, using the optodroplet assay 42 , which relies on light activation of the Cry2 dimerization domain to trigger condensation (Figs S5a and S5b) and which we previously used to implicate protein domains in biomolecular condensation 30 . Coilin FL makes Cajal bodies without optical activation and additional puncta after induction, as expected (Fig.…”

“…The N-and C-terminal domains (NTD and CTD, respectively) are the most highly conserved; they are separated by a region of low complexity that is poorly conserved and likely intrinsically disordered. This middle domain contains a bipartite nuclear localization signal (NLS) and an RG box modified by dimethylarginine and bound by the spinal motor neuron protein (SMN) tudor domain 11,[27][28][29][30] . The coilin CTD harbors its own tudor domain, which interestingly lacks the aromatic amino acids that would enable it to bind dimethylarginine 31 .…”