RT Journal Article
SR Electronic
T1 RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 273912
DO 10.1101/273912
A1 Mark A. McClintock
A1 Carly I. Dix
A1 Christopher M. Johnson
A1 Stephen H. McLaughlin
A1 Rory J. Maizels
A1 Ha Thi Hoang
A1 Simon L. Bullock
YR 2018
UL http://biorxiv.org/content/early/2018/02/28/273912.abstract
AB 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 stabilises 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.