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

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 events occur coincidently with the differentiation of myoblasts into myotubes and concomitant with the expression of uniquely long muscle-specific transcripts. We show that NE buds are derived from the inner nuclear membrane, contain internal vesicles, and they are specifically enriched with long sarcomeric transcripts. Moreover, we demonstrate the role for an RNA-binding protein and membrane remodeling factors in mRNA targeting to NE buds and NE bud biogenesis. Our findings uncover with mechanistic insight a non-canonical pathway for large transcript packaging and export in muscles cells.