Polarised mRNA transport is a prevalent mechanism for spatial control of protein
synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the
regulation of their movement are poorly understood. We have reconstituted microtubule minus
end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein
and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by
the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent
RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a
cis-acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the
latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based
on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor
protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport