TY - JOUR
T1 - Single mRNA molecules demonstrate probabilistic movement in living mammalian cells
AU - Fusco, Dahlene
AU - Accornero, Nathalie
AU - Lavoie, Brigitte
AU - Shenoy, Shailesh M.
AU - Blanchard, Jean Marie
AU - Singer, Robert H.
AU - Bertrand, Edouard
N1 - Funding Information:
We thank A. Femino for her help with the quantification of the number of probes per molecule, and we also thank Pierre Travo and the Imaging Facility of IFR 24. This work was supported by grants from L'Association pour la Recherche contre le Cancer (l'ARC) (9043) and the Ministère de la Recherche Française et de la Technologie (Action Concertée Incitative) to E.B. and by National Institutes of Health grant GM54887 to R.H.S. N.A. was supported by a fellowship from l'ARC, La Ligue, and Sidaction. D.F. is supported by the Albert Einstein Medical Scientist Training Program. The authors declare that they have no competing financial interests.
PY - 2003/1/21
Y1 - 2003/1/21
N2 - 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 [1-4]. 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 β-actin mRNA zipcode increased both the frequency and length of these movements, providing a common mechanistic basis for both localized and non-localized 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.
AB - 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 [1-4]. 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 β-actin mRNA zipcode increased both the frequency and length of these movements, providing a common mechanistic basis for both localized and non-localized 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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U2 - 10.1016/S0960-9822(02)01436-7
DO - 10.1016/S0960-9822(02)01436-7
M3 - Article
C2 - 12546792
AN - SCOPUS:0347156907
SN - 0960-9822
VL - 13
SP - 161
EP - 167
JO - Current Biology
JF - Current Biology
IS - 2
ER -