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bioRxiv · 10.64898/2026.01.23.701081

Super-resolved imaging of mRNA ultrastructure in cells

Passera, A.·Welzl, P.·Gomez-Segalas, A.·Plaschka, C.·Balzarotti, F.
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Abstract

Messenger RNA (mRNA) is a central polymer of gene expression, whose ultrastructure and defining regulatory rules remain unclear. To visualize the ultrastructure of mRNA, we here develop Combi-PAINT, a powerful and generalizable method for combinatorial super-resolved DNA-PAINT multiplexing, which we combine with high-efficiency RNA labelling and MINFLUX microscopy. This approach enables the nanometer-precision tracing of mRNA in three dimensions in cells. We use Combi-PAINT to visualize multiple distinct mRNA species inside the human cell nucleus and cytoplasm, revealing their quantitative ultrastructures and transcript-specific molecular patterns. By bridging sequence specificity with nanometer resolution, we provide a new lens for studying the cellular life of mRNA.

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Passera, A., Welzl, P., Gomez-Segalas, A., Plaschka, C., Balzarotti, F.. 2026-01-23. Super-resolved imaging of mRNA ultrastructure in cells. https://doi.org/10.64898/2026.01.23.701081

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