Localization of cofilin mRNA to the leading edge of migrating cells promotes directed cell migration

Abstract

mRNA trafficking, which enables the localization of mRNAs to particular intracellular targets, occurs in a wide variety of cells. The importance of the resulting RNA distribution for cellular functions, however, has been difficult to assess. We have found that cofilin-1 mRNA is rapidly localized to the leading edge of human lung carcinoma cells and that VICKZ family RNA-binding proteins help mediate this localization through specific interactions with the 3'UTR of cofilin mRNA. Using a phagokinetic assay for cell motility, we have been able to quantify the effect of mRNA localization on the rescue of lung carcinoma cells in which cofilin was knocked down by using short hairpin RNA (shRNA). Although restoring cofilin protein to normal endogenous levels rescues general lamellipodia formation around the periphery of the cell, only when the rescuing cofilin mRNA can localize to the leading edge is it capable of also fully rescuing directed cell movement. These results demonstrate that localization of an mRNA can provide an additional level of regulation for the function of its protein product.