RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Stephen H McLaughlin
Funding
Medical Research Council (MC_U105178790)
- Mark A McClintock
- Carly I Dix
- Christopher M Johnson
- Stephen H McLaughlin
- Rory J Maizels
- Ha Thi Hoang
- Simon L Bullock
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, McClintock et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs
eLife 7:e36312.
https://doi.org/10.7554/eLife.36312
