David Grunwald, RNA Therapeutics Institute, Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School
Host: Warren Zipfel
Visualizing mRNA and DNA repeats to study nuclear dynamics and export of mRNAs
More than 99.99% of proteins are encoded by nuclear DNA. This makes the export of mRNA to the cytoplasm for use in protein translation essential to gene expression and cellular function. Not surprisingly mRNA export is disrupted in multiple diseases and is targeted by viruses to improve viral replication and survival. mRNA export occurs through nuclear pore complexes (NPCs), which act as molecular “gateways” for the exchange of protein and RNA across the nuclear envelope. While much is known about the directional transport of proteins via karyopherins and the cellular Ran gradient, much less is known about the molecular mechanism and regulation of mRNA export, which functions independently of the Ran system.
We study the real life dynamics of molecules in the cell nucleus and during nucleocytoplasmic transport using multiple model mRNAs (housekeeping, induced, viral) and cell systems (human, mouse and yeast). We do so on the one hand by developing using single molecule real time microscopy in 2D and simultaneous 3D to bypass the limits of diffraction. On the other hand, we develop and optimize ways to label the nuclear landscape using RNA aptamers and CRISPR based DNA labeling technology, paying special attention to performance characteristics and metrics.
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