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RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.


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.

SUBMITTER: McClintock MA 

PROVIDER: S-EPMC6056234 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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RNA-directed activation of cytoplasmic dynein-1 in reconstituted transport RNPs.

McClintock Mark A MA   Dix Carly I CI   Johnson Christopher M CM   McLaughlin Stephen H SH   Maizels Rory J RJ   Hoang Ha Thi HT   Bullock Simon L SL  

eLife 20180626


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 comple  ...[more]

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