Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 29 November 2005
Vol. 2005, Issue 312, p. tw422
[DOI: 10.1126/stke.3122005tw422]


TRANSLATION Zipping Up Targeting and Translation

Targeting messenger RNA (mRNA) transcripts to the appropriate subcellular location provides a mechanism for optimizing production of a particular protein at the right place and the right time. Zipcode binding protein 1 (ZBP1) binds to the "zipcode" sequence in the β-actin mRNA transcript, promoting its translocation to sites of actin polymerization, such as growth cones or the leading edge of migrating fibroblasts. Hüttelmaier et al. found that, in differentiated NG108-15 neuroblastoma cells, ZBP1 labeled with green fluorescent protein colocalized with β-actin mRNA in the nucleus as well as at the leading edge, along neurites, and in filopodia. ZBP1 inhibited translation of β-actin in rabbit reticulocyte lysates and, in cells, ZBP1 knockdown with siRNA enhanced translation of a reporter containing the β-actin 3' region in a manner that depended on the presence of the zipcode sequence. Sequence analysis indicated that ZBP1 contained a possible SH3-binding motif that might function as a Src tyrosine kinase docking site. Indeed, Src phosphorylated ZBP1 on Tyr 396 both in vitro and in cells. Increased Src activity promoted translation of a zipcode-containing reporter, and analysis of nonphosphorylatable or phosphorylation-mimicking mutants indicated that ZBP1 phosphorylation decreased its association with β-actin mRNA. FRET analysis indicated that Src associated with ZBP1 in growth cones and near filopodia. ZBP1 knockdown interfered with neurite outgrowth; this could be rescued by phosphorylatable ZBP1 but not by the nonphosphorylatable mutant. Thus, the authors conclude that ZBP1 not only regulates β-actin localization but also prevents its premature translation until reaching an appropriate locale and undergoing phosphorylation by Src. Dahm and Kiebler provide context in a News and Views article.

S. Hüttelmaier, D. Zenklusen, M. Lederer, J. Dictenberg, M. Lorenz, X. Meng, G. J. Bassell, J. Condeelis, R. H. Singer, Spatial regulation of β-actin translation by Src-dependent phosphorylation by ZBP1. Nature 438, 512-515 (2005). [PubMed]

R. Dahm, M. Kiebler, Silenced mRNA on the move. Nature 438, 432-435 (2005). [PubMed]

Citation: Zipping Up Targeting and Translation. Sci. STKE 2005, tw422 (2005).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882