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Cytoplasmic
mRNA movements ultimately determine the spatial distribution of protein
synthesis. Although some mRNAs are compartmentalized in cytoplasmic
regions, most mRNAs, such as housekeeping mRNAs or the poly-adenylated
mRNA population, are believed to be distributed throughout the cytoplasm.
The general mechanism by which all mRNAs may move, and how this may
be related to localization, is unknown. Here, we report a method to
visualize single mRNA molecules in living mammalian cells, and we report
that, regardless of any specific cytoplasmic distribution, individual
mRNA molecules exhibit rapid and directional movements on microtubules.
Importantly, the beta-actin mRNA zipcode increased both the frequency
and length of these movements, providing a common mechanistic basis
for both localized and nonlocalized mRNAs. Disruption of the cytoskeleton
with drugs showed that microtubules and microfilaments are involved
in the types of mRNA movements we have observed, which included complete
immobility and corralled and nonrestricted diffusion. Individual mRNA
molecules switched frequently among these movements, suggesting that
mRNAs undergo continuous cycles of anchoring, diffusion, and active
transport. |
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