Nuclear speckles (NS) enhance the expression of NS-associated genes, possibly by elevating local levels of factors involved in multiple steps of gene expression. While dozens of large NS are distributed throughout interchromatin regions, the extent to which NS components dynamically redistribute between NS to adjust to local physiological demands remains unknown. Here, we used live-cell imaging of endogenous NS proteins to identify an interchromatin network of connections that functionally link NS throughout the nucleus. Over timescales ranging from tens of seconds to minutes, NS material is transferred through these curvilinear connections, rather than through isotropic exchange across the NS/nucleoplasm interface followed by diffusion in all directions throughout the nucleoplasm as predicted by current models. Multiphase NS-connecting structures form through the dynamic juxtapositions of multiple NS component phases. Each phase exhibits distinct yet recurrent dynamic patterns, but together, they integrate into a more stable, multiphase, NS-connecting structure in an ATP- and transcription-dependent manner. Our findings reveal the existence of a cellular mechanism that facilitates coordinated inter-NS protein trafficking through multiphase connections.
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Kim et al. (2026) studied this question.