Nuclear envelope budding enables export of large transcripts in muscle cells

Area of Science:

• Cell Biology
• Molecular Biology
• Muscle Biology

Background:

• Nuclear envelope budding (NEB) is an alternative nuclear export route for large viral particles.
• The role of NEB for large endogenous cargoes in mammalian cells is largely unexplored.

Purpose of the Study:

• To investigate the significance of NEB for large endogenous cargoes in mammalian cells.
• To elucidate the mechanism of NEB-mediated nuclear export of muscle-specific transcripts.

Main Methods:

• Electron microscopy
• Fluorescence microscopy
• Biochemical assays

Main Results:

• NEB events occur during myoblast differentiation into myotubes, coinciding with the expression of long muscle-specific transcripts.
• NE buds originate from the inner nuclear membrane, contain internal vesicles, and are enriched with long sarcomeric transcripts.
• The protein UAP56-interacting factor (UIF) regulates mRNA cargo targeting into NE buds, and the pathway requires the ESCRT-III machinery.

Conclusions:

• A non-canonical pathway for large transcript nuclear export exists in muscle cells.
• This pathway involves NEB and is crucial for exporting extremely long muscle-specific transcripts during differentiation.