Niewidok et al. analyze the distribution and dynamics of RNA-binding proteins (RBPs) with single-molecule resolution in living neuronal cells, providing direct support for liquid droplet behavior of stress granules in living cells and revealing transient binding of RBPs in nanocores.

Background: RNA protein granules regulate mRNA translation and are involved in neurodegeneration. Results: Induction of RNA protein granules by G3BP1 or IMP1 changes the amount of long and short tau mRNA and protein. Conclusion: RNA protein granules differentially affect tau isoform expression.Significance: This is the first report showing that RNP granules modulate tau isoform expression, potentially linking RNP granule formation to tauopathies.

Highlights 3D-polymerized cell dispersions allow evaluation of tissue clearing protocols Protein fluorescence retention can be tested during tissue clearing A semi-automated random walker enables segmentation of memory exceeding image data

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