Nuclear envelope budding is a non-canonical mechanism to export large transcripts in muscle cells

S Zaganelli, JB Meehl, RG Abrisch & Gia Voeltz*

*University of Colorado, Department of Molecular, Cellular and Developmental Biology, Boulder, CO, USA, gia.voeltz@colorado.edu

The nuclear pore complex (NPC) is considered the sole route to transport molecules across the nuclear envelope (NE). In recent years, NE budding (NEB) has emerged as an alternative route for nuclear export of viral particles that are too large to pass through the NPC. Yet, the significance of this unconventional export pathway for large endogenous cargoes in mammalian cells has remained largely unexplored. Here, we use a combination of electron and fluorescence microscopy to demonstrate that NEB occurs concomitantly with the differentiation of myoblasts into myotubes. We show that NE buds are derived from the inner nuclear membrane, contain internal vesicles, and are enriched with long sarcomeric transcripts. We identify the RNA-binding protein UIF and the ESCRTIII membrane remodeling machinery function to traffic these large mRNA cargoes into NE buds for nuclear egress. Together these data reveal a non-canonical pathway for large transcript packaging and export in muscles cells.

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