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PLoS Genet. 2016 Jul 27;12(7):e1006192. doi: 10.1371/journal.pgen.1006192. eCollection 2016 Jul.

Tracking the Fragile X Mental Retardation Protein in a Highly Ordered Neuronal RiboNucleoParticles Population: A Link between Stalled Polyribosomes and RNA Granules.

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Institut universitaire en santé mentale de Québec, Quebec, Canada.
Département de Psychiatrie et de Neurosciences, Faculté de Médecine, Université Laval, Québec, Quebec, Canada.
Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, Université de Nice-Sophia Antipolis, F-06560 Valbonne, France.
Neuroscience Institute, Department of Neuroscience and Physiology, New York University, New York, New York, United States of America.
Centre de recherche en biologie de la reproduction, Département des sciences animales, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, Québec, Quebec, Canada.
Département de Biochimie, Microbiologie et Bio-Informatique, Université Laval, Québec, Quebec, Canada.


Local translation at the synapse plays key roles in neuron development and activity-dependent synaptic plasticity. mRNAs are translocated from the neuronal soma to the distant synapses as compacted ribonucleoparticles referred to as RNA granules. These contain many RNA-binding proteins, including the Fragile X Mental Retardation Protein (FMRP), the absence of which results in Fragile X Syndrome, the most common inherited form of intellectual disability and the leading genetic cause of autism. Using FMRP as a tracer, we purified a specific population of RNA granules from mouse brain homogenates. Protein composition analyses revealed a strong relationship between polyribosomes and RNA granules. However, the latter have distinct architectural and structural properties, since they are detected as close compact structures as observed by electron microscopy, and converging evidence point to the possibility that these structures emerge from stalled polyribosomes. Time-lapse video microscopy indicated that single granules merge to form cargoes that are transported from the soma to distal locations. Transcriptomic analyses showed that a subset of mRNAs involved in cytoskeleton remodelling and neural development is selectively enriched in RNA granules. One third of the putative mRNA targets described for FMRP appear to be transported in granules and FMRP is more abundant in granules than in polyribosomes. This observation supports a primary role for FMRP in granules biology. Our findings open new avenues for the study of RNA granule dysfunctions in animal models of nervous system disorders, such as Fragile X syndrome.

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