Heterogeneous distribution of cellular components is at the core of establishing asymmetry and polarity within cells; this can be achieved by selective localisation of proteins to specific regions of the cytoplasm and also through localised mRNA expression. Here (p. ), Joel Yisraeli, Yael Maizels and colleagues combined live cell imaging with genetic and biochemical approaches to investigate the mechanism and function of localised cofilin mRNA expression in the H1299 human lung cancer cell line. Cofilin binds to and destabilises actin filaments and, as such, is often recruited to structures that necessitate dynamic remodelling of the actin network. The authors demonstrated that, although cofilin mRNA was localised throughout the cytoplasm in non-motile cells, it became enriched in lamellipodia when cell migration was induced. Interestingly, this effect is mediated by the 3′-untranslated region (UTR) of cofilin mRNA. As shown here, members of the VICKZ family of RNA-binding proteins bound to the 3′UTR of cofilin mRNA and this interaction was required for its lamellipodial localisation. Furthermore, knockdown of cofilin inhibited the formation of lamellipodia but this could be overcome by introducing cofilin mRNA lacking the 3′UTR; however, the resulting cells were not capable of directed cell mobility despite having lamellipodia. Therefore, this study highlights how the regulation of mRNA localisation can contribute to the function of a protein in specific cellular processes.
