UMass Chan Medical School Faculty Publications

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Department of Neurobiology; Department of Biochemistry and Molecular Pharmacology; Budnik Lab; Graduate School of Biomedical Sciences, Neuroscience Program

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Nuclear Envelope; Molecular Chaperones; Ribonucleoproteins; Dystonia


Biochemistry, Biophysics, and Structural Biology | Molecular and Cellular Neuroscience


A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown. Here, we identify Torsin, an AAA-ATPase that in humans is linked to dystonia, as a major mediator of primary megaRNP envelopment during NE budding. In torsin mutants, megaRNPs accumulate within the perinuclear space, and the messenger RNAs contained within fail to reach synaptic sites, preventing normal synaptic protein synthesis and thus proper synaptic bouton development. These studies begin to establish the cellular machinery underlying the exit of megaRNPs via budding, offer an explanation for the "nuclear blebbing" phenotype found in dystonia models, and provide an important link between Torsin and the synaptic phenotypes observed in dystonia.

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Copyright © 2013 The Authors. Published by Elsevier Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version



Cell Rep. 2013 Apr 25;3(4):988-95. doi: 10.1016/j.celrep.2013.03.015. Link to article on publisher's site


Authors Vahbiz Jokhi and James Ashley are doctoral students in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.

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Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.