Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1.
Localization of beta-actin messenger RNA to sites of active actin polymerization modulates cell migration during embryogenesis, differentiation and possibly carcinogenesis. This localization requires the oncofetal protein ZBP1 (Zipcode binding protein 1), which binds to a conserved 54-nucleotide element in the 3'-untranslated region of the beta-actin mRNA known as the 'zipcode'. ZBP1 promotes translocation of the beta-actin transcript to actin-rich protrusions in primary fibroblasts and neurons. It is not known how the ZBP1-RNA complex achieves asymmetric protein sorting by localizing beta-actin mRNA. Here we show that chicken ZBP1 modulates the translation of beta-actin mRNA. ZBP1 associates with the beta-actin transcript in the nucleus and prevents premature translation in the cytoplasm by blocking translation initiation. Translation only occurs when the ZBP1-RNA complex reaches its destination at the periphery of the cell. At the endpoint of mRNA transport, the protein kinase Src promotes translation by phosphorylating a key tyrosine residue in ZBP1 that is required for binding to RNA. These sequential events provide both temporal and spatial control over beta-actin mRNA translation, which is important for cell migration and neurite outgrowth.
Hüttelmaier
Stefan
S
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA. stefan.huettelmaier@medizin.uni-halle.de
Zenklusen
Daniel
D
Lederer
Marcell
M
Dictenberg
Jason
J
Lorenz
Mike
M
Meng
Xiuhua
X
Bassell
Gary J
GJ
Condeelis
John
J
Singer
Robert H
RH
D000199:Actins / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D002645:Chickens; D004268:DNA-Binding Proteins; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D014176:Protein Biosynthesis; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D030161:Avian Proteins; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C498636:ZBP1 protein, Gallus gallus; C485731:ZBP1 protein, human; D016392:Proto-Oncogene Proteins pp60(c-src)