Torsin Mediates Primary Envelopment of Large Ribonucleoprotein Granules at the Nuclear Envelope

• Published in: Cell reports (Cambridge) 2013-04, Vol.3 (4), p.988-995
• Main Authors: Jokhi, Vahbiz, Ashley, James, Nunnari, John, Noma, Akiko, Ito, Naoto, Wakabayashi-Ito, Noriko, Moore, Melissa J., Budnik, Vivian
• Format: Article
• Language: English
• Subjects: Animals; Budding; Cell Nucleus - metabolism; Cells, Cultured; Drosophila; Dystonia - metabolism; Humans; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Mutation; Nuclear Envelope - metabolism; Nuclear Envelope - ultrastructure; Ribonucleoproteins - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2013.03.015

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. [Display omitted] •Large RNPs (megaRNPs) can exit the nucleus via nuclear envelope budding•The dystonia-linked AAA-ATPase Torsin is required for nuclear exit of megaRNPs•Torsin is involved in scission of the inner nuclear membrane during megaRNP egress•torsin mutants have decreased postsynaptic mRNAs and proteins and abnormal synapses Nuclear export of ultralarge RNPs via nuclear envelope budding was recently observed, but the mechanisms underlying this process are unknown. Budnik and colleagues now find that Torsin is involved in scission of the inner nuclear membrane during nuclear envelope budding.