Published online 30 December 2002. doi:10.1083/jcb1601iti4
© The Rockefeller University Press,
0021-9525/2003/1/7-b $5.00
The Journal of Cell Biology, Volume 160, Number 1, 7-b-7
RNA travels with ZBP1
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Lamella-localized ZBP1 (white) granules do not form if ZBP1 cannot bind actin mRNA (right).
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On page 77, Farina et al. get a handle on RNA localization machinery by proving that an RNA-binding protein is essential for both mRNA transport and cell motility.
The cell motility connection comes about because localization of the ß-actin mRNA to the lamellae is required for cell polarity and motility in fibroblasts. The new results show that this localization depends on ZBP1, a protein associated with cytoplasmic granules that contain the actin mRNA. ZBP1 bound to the mRNA through two COOH-terminal KH domains that were required for granule formation and attachment to the actin cytoskeleton. NH2-terminal regions of ZBP1 were necessary for granule localization in the lamellae.
Dominantnegative ZBP1 constructs that mislocalized actin RNA inhibited fibroblast motility. Since mRNAs for some actin-associated proteins, such as ARP3, also contain ZBP1-binding sequences, the authors believe that ZBP1 may link several messages involved in motility to a transport complex. But ZBP1 may be more than just a scaffold: a ZBP1 homologue has been linked to translational repression of the insulin-related growth factor. Perhaps ZBP1 also ensures that the actin mRNA is not translated until it reaches its ultimate destination.The group plans to purify ZBP1- associated proteins in the complex to identify the motor responsible for actin-based transport. ZBP1 is also known to be associated with microtubules in neurons, so it may connect to different motors depending on the cell type.
Nicole LeBrasseur
lebrasn{at}rockefeller.edu

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Two ZBP1 KH domains facilitate ß-actin mRNA localization, granule formation, and cytoskeletal attachment
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