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Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1
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Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1
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Journal Article
Spatial regulation of β-actin translation by Src-dependent phosphorylation of ZBP1
2005
Overview
Localization of β-actin messenger RNA to sites of active actin polymerization modulates cell migration during embryogenesis, differentiation and possibly carcinogenesis
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. 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 β-actin mRNA known as the ‘zipcode’. ZBP1 promotes translocation of the β-actin transcript to actin-rich protrusions in primary fibroblasts and neurons
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. It is not known how the ZBP1–RNA complex achieves asymmetric protein sorting by localizing β-actin mRNA. Here we show that chicken ZBP1 modulates the translation of β-actin mRNA. ZBP1 associates with the β-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 β-actin mRNA translation, which is important for cell migration and neurite outgrowth.
Publisher
Nature Publishing Group UK,Nature Publishing
Subject
/ Animals
/ Biological and medical sciences
/ Chickens
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ letter
/ Molecular and cellular biology
/ Proto-Oncogene Proteins pp60(c-src) - metabolism
/ RNA, Small Interfering - genetics
/ RNA, Small Interfering - metabolism
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - metabolism
/ Science
